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Protein & Peptide Letters, 2016, 23, 1-14 1
0929-8665/16 $58.00+.00 © 2016 Bentham Science Publishers
Cryptic Peptides from Collagen - A Critical Review
Pradipta Banerjeea and C. Shanthib*
aPresently in Department of Life Science, Dayananda Sagar Institution, Bangalore-560078, India;
bSchool of Bio Sciences and Technology, Vellore Institute of Technology, Vellore- 632014
Abstract: Collagen, a predominant structural protein in extracellular matrix (ECM ), is now consid-
ered to have probable roles in many biological activities and hence, in different forms have found ap-
plication as nutraceutical or pharmaceutical therapy option. Many of the biological properties are be-
lieved to be due to small hidden peptide residues in the collagen molecules, which come into play after
the biodegradation or biosorption of the parent molecule. These peptide regions are called cryptic pep-
tides or by some, as cryptides. The proteolytic hydrolysis of the ECM protein releases the cryptic pep-
tides with many novel biological activities not exhibited directly by the parental protein which include
angiogenic, antimicrobial, mitogenic and chemotactic properties. The research for understanding the role of these cryptic
peptide regions and making use of them in medical field is very active. Such an understanding could lead to the develop-
ment of peptide supplements for many biomedical applications. The prolific research in this area is reviewed in this paper.
Keywords: Collagen peptides, cryptic peptides, ECM peptides, bioactive peptides.
Received: ????? 11, 2015 Revised: ??????? 21, 2015 Accepted: ???????? 16, 2016
1. INTRODUCTION
Collagen is a predominantly occurring bio-polymer in
ECM that is essential for the structural integrity of most or-
gans [1]. It represents the major structural protein accounting
for approximately 30% (dry weight) of all vertebrate body
proteins. More than 90% of the extracellular proteins in the
tendon and bone and >50 % in the skin consist of collagen.
Till date, 28 well-defined types of vertebrate collagen have
been identified. They are broadly classified into fibrillar
(types I, II, II, V, XI, XXIV and XXVII), fibril-associated
(types IX, XII, XIV, XVI, XIX, XX, XXI, and XXII), net-
work forming (types IV, VIII and X) and transmembrane
collagens (type XIII, XVII, XXIII and XXV). A well-known
triple helical structural feature of collagen is due to the re-
peating Gly-X-Y triplets, where X is mainly proline and Y is
mainly hydroxyproline [2]. Other amino acids can occupy
these positions without significantly altering collagen struc-
ture [3, 4].
The triple helical structure of collagen and its biocom-
patible nature has made it a widely used biomaterial [5, 6].
The most abundant fibrillar collagen type I has found appli-
cation in many restorative and replacement surgeries ranging
from wound healing to heart valve repair [5-8]. The forms of
collagen used vary from films, sponges to hydrogels by
variation in extraction, solubilization and crosslinking proce-
dures [9, 10]. Collagen is employed as key material or as a
composite in 3D scaffolds for tissue engineering [11-14].
*Address correspondence to this author at the School of Bio Sciences and
Technology, Vellore Institute of Technology, Vellore- 632014; Tel: +91 416
220 2549; Fax: +91 416 2243091; E-mail: cshanthi@vit.ac.in
The performance of collagen-based scaffolds has further
been improved by different fabrication procedures and also
by immobilizing growth factors [9]. The need for biodegrad-
able and non-degradable scaffolds for various implants has
been facilitated by the use of denatured and cross-linked
collagen.
While biological scaffolds based on ECM protein such as
collagen have been used in reconstructive surgery for tissue
repair and remodeling, the exact mechanism of action of the
protein part is not well understood [14]. However, the prote-
olytic degradation of ECM scaffold and the progenitor cells
recruitment are considered important steps in the tissue re-
construction and remodeling process [15]. The proteolytic
degradation leads to release of peptides with novel biological
activities such as angiogen ic, antimicrobial, mitogenic and
chemotactic properties not directly exhibited by the intact
parent protein [16]. These peptides are called cryptic pep-
tides. Before discussing about the cryptic peptides, the re-
search work carried out in fields like food and pharmaceuti-
cals for identifying the uses of collagen hydrolysates and
peptides is reviewed [17].
2. NEW DEVELOPMENTS
2.1. Collagen Peptides as Food Additives
Gelatin, degraded collagen from bone and skin, is used
for imparting special texture to food [18]. Damodaran et al.
studied the inhibitory role of collagen peptides in crystalliza-
tion of ice cream mix. Using molecular dynamic simulation,
the peptide GPAG was found to be more effective in retard-
ing ice crystal growth than peptide GGAG suggesting that
C. Shanthi
2 Protein & Peptide Letters, 2016, Vol. 23, No. 7 Banerjee and Shanthi
the collagen peptide could be used as an antifreeze agent
[19]. Freeze dried lactic acid bacteria had been shown to
improve their survival rate when lyophilized with antifreeze
peptides in collagen hydrolysate [20].
2.2. Collagen Peptides for Health
Collagen is used as a supplement to rejuvenate aging
skin. Several forms of collagen as hydrolysate and as low
molecular weight peptides from different sources have found
use as nutraceuticals [21, 22]. Collagen hydrolysate is also
used as health supplement for improving cartilage and bone
health in joint diseases [22]. These peptides have been found
to promote collagen synthesis [23]. Collagen peptides fed to
mature rats improve their bone mineral density [24, 25]. Pro-
pyl hydroxyproline dipeptide detected in guinea pig blood
fed with collagen hydrolysate stimulates hyaluronic acid in
cultured synovial cells [26]. Enzymatically hydrolyzed col-
lagen peptides have been found to be analgesic and anti-
inflammatory [27].
Conventionally, collagen has been used in the pharma-
ceutical industry as a drug carrier. Due to good hydrating and
wound healing properties, collagen has been used in skin
lotions and moisturizers. Intravenous injection of collagen
peptide increases biosynthesis of collagen and improves
wound healing in guinea pigs [28]. Collagen from hydro-
lysates has found application in skin formulations [29]. In-
gestion of collagen hydrolysate improved bone mineral den-
sity in undernourished mice [22]. Daily intake of collagen
hydrolysate improves arthritic condition in patients [30]. The
sources of these collagens are originally bovine and pig skins
but fear of mad cow d isease has changed the focus to fish
skin and scales [16, 31 & 32]. Large amount of collagen and
gelatin from slaughter house and fish wastes which initially
was used as feed supplement, later found application as
therapeutics with the advancement in peptide research and
related techniques [33, 34]. Collagen peptides were charac-
terized and their therapeutic properties like antioxidant and
ACE inhibition were determined (Table 1 and 2).
As collagen is part of the extracellular matrix, its prob-
able role in cell maintenance and growth in addition to me-
chanical support led to identification of bioactive regions and
use of these peptides in tissue engineering matrices [35, 36].
Collagen peptide immobilized on CMC K carrageenan was
found to promote wound healing [37]. Peptides forming col-
lagen hydrolysates like Gly-Leu-Pro-Leu-Hyp, Pro-Hyp, and
Hyp-Gly promoted differentiation of mesendoderms in
mouse embryonic stem cells [38, 39]. Findings on the ap-
pearance of collagen peptides in blood after ingestion of col-
lagen hydrolysate instigated further research on the effect or
probable role of these peptides [40, 41].
2.3. Cryptic Peptides
The word ‘cryptic’ derived from the Greek word ‘krypti-
kos’ indicates concealment. In the context of proteins, the
word refers to the functional sequences that are buried inside
the structure of macromolecules and therefore are ‘con-
cealed’ [42]. New data indicate that regions with biological
activity could be hidden inside virtually any large protein
molecule. In most cases, these peptides with divergent bio-
logical activities remain in an “inactivated” state within the
parent protein and cannot be predicted from either the amino
acid sequence or the activity of the parent protein [42, 43].
The cryptic subset of peptides, residing within the larger
proteome, has been termed holistically as the ‘cryptome’ and
it potentially represents every single bioactive peptide having
an array of bioactivities. Matrikine and matricriptines are the
terms coined to denote peptides derived from ECM with
biological activity [44]. These peptides elicit varied biologi-
cal activities such as regulation of synthesis and degradation
of matrix, wound healing, angiogenesis, antitumor activities,
immune response and so on [44-50]. The regulation of the
peptide activity is yet to be understood at its entirety. Most
physiological regulatory systems follow a feedback pattern
regulation [51].
Activation of these cryptic moieties requires the chemical
or physical processing of macromolecule possessing bioac-
tive units, which may be furnished by conformational change
or proteolytic cleavage [51-53]. Either of these processes can
expose or ‘unmask’ the cryptic site, which in turn, becomes
available for execution of its function. Conformational
changes can be brought about in most ECM molecules by
filament-generated tension, mechanical shear, or interaction
with other ECM components [54-57]. Cell alignment on fi-
bronectin polymers occurs through exposure of a cryptic, cell
adhesive receptor binding domain in the fibronectin se-
quence. Chemical processing of collagen can only occur
through a distinct set of matrix metalloproteinases (MMP)
initiated action followed by serine proteases [54, 55].
The bioactive peptides produced by proteolytic process-
ing are broken down by a battery of proteases produced by
the cells [56]. The bioactive peptides come into existence for
a short period of time in which they are functional, followed
by fragmentation by peptidases. For example, cathepsin L
can generate endostatin from collagen, but along with
cathepsin D, is also responsible for its degradation [56]. This
mode of regulation is schematically presented in Fig. 1.
Bioactive peptides, whose activities depend on conforma-
tional ‘unmasking’, are probably regulated by tensional
forces [57]. More than 50% of the cryptic self-association
sites in fibronectin that are necessary for polymerization are
located in a module of fibronectin without disulfide bonds,
thus allowing reversible unfolding with certain flexibility
[58]. This ensures a quick and consistent response to cell-
generated tension. But such sites often remain masked until a
proper physiological stimulus is generated at a certain point
[59]. Similarly, collagen type I contains the cell adhesive
RGD motif, which in native collagen fails to attach the same
number of cells as in denatured collagen. In the latter sce-
nario, the triple helical arrangement has been disrupted, lead-
ing to the exposure of the previously hidden RGD and possi-
bly other sites [60-62].
The amino acid sequence of an exposed bioactive peptide
is possibly the single most important aspect which defines its
unique bioactivity [61]. However, studies in sequences of
peptides till date are yet to reveal some underlying common-
alities between peptides displaying a single activity [62].
With increased use of collagen hydrolysate as nutraceutics
and pharmaceutics, research in this field started focusing on
identifying the biological role of cryptic regions in collagen
and employing them in designing 3D scaffolds [63-66].
Cryptic Peptides from Collagen - A Critical Review Protein & Peptide Letters, 2016, Vol. 23, No. 7 3
2.4. Cryptic Regions in Collagen
Collagen and several other proteins comprise of smaller
segments that when proteolytically excised, have been
shown to act as independent modulators of specific physio-
logical parameters [67,68]. A 20 kDa C-terminal fragment of
collagen XVIII has been reported to display potent anti-
angiogenic activity [67]. A 22 kDa fragment, termed as
‘restin’ has been isolated from the non-triple helical domain
of collagen XV with similar activity [68]. The non-triple
helical C-terminal domains of type IV have been reported to
be potent sources of bioactivities. Three fragments isolated
from the three polypeptide chains of this type of collagen,
termed as arresten, canstatin and tumstatin have been re-
ported to display anti-angiogenic and anti-tumor properties
[69-75]. Cryptic regions in collagen types are tabulated in
Table 1.
2.5. Antioxidative Peptides from Collagen
Many health disorders like cancer, diabetes, cardiovascu-
lar disease, Alzheimer’s etc. result when the normal antioxi-
dant system in the body cannot cope up with excessive gen-
eration of free radicals [79-81]. Recently, there is a lot of
awareness on the use of safer, preferably natural antioxidants
to prevent diseases [82-84]. The role of antioxidants from
foods in improving life expectancy has triggered studies on
antioxidants containing foods from different countries [83,
84]. As food proteins are known to inhibit lipid peroxidation,
the antioxidant properties of peptides arising from these pro-
teins have been intensely studied. Peptides from enzyme
hydrolysates of discarded fish processing wastes exhibit an-
tioxidant property [85]. Collagen containing wastes from
slaughter houses are considered valuable sources of antioxi-
dants and many antioxidant peptides have been identified
from the hydrolysates of fish and animal wastes (Table-2).
Several proteases of microbial, plant and animal origin with
different cleavage sites have been used to hydrolyze collagen
to varying sized peptides with bio activity. The sequence,
composition, positioning of amino acids and molecular
weight determine the biological role of the peptide [86-89].
Antioxidant peptides from Alaska pollack skin, jumbo squid
skin gelatin, tuna backbone protein and thornback ray skin
contain sequences with glycine at the C terminal end and a
repeating Gly-Pro-X. Although collagen contains a repeating
Gly-X-Y, a number of antioxidant peptides have been identi-
fied and the details with appropriate references are tabulated
in Table 2. Presence of certain amino acids like Y, F, W, H,
M, C and position of proline in the peptides have been impli-
cated to impart chelating and scavenging free radicals. Pep-
tides with charged amino acids from Nile tilapia skin gelatin,
cobia gelatin, porcine skin collagen, bullfrog skin and tuna
backbone have good scavenging properties [90-92]. Peptides
isolated from chicken skin hydrolysate and thornback ray
skin hydrolysate have a synergistic antioxidant activity when
used in combination and the reasons for this synergy need
further study [87].
2.6. Angiotensin Converting Enzyme (ACE) Inhibitory
Collagen Peptides
ACE catalyzes degradation of bradykinin, a hypertension
lowering peptide and hence, ACE inhibitory agents have
been screened to control hypertension [102-104]. Currently
used antihypertensive drugs have several side effects. This
has initiated search for newer ACE inhibitory peptides de-
rived from plant and animal sources [105] with collagen pep-
tides being no exception. Almost all ACE inhibitory peptides
contain 10 -12 amino acids with a hydrophobic C terminal
[106]. Collagen contains Gly-X-Y repeating sequences and
hence ACE inhibitory peptides may be present in regions
where X is often a Pro, Leu, Ile or Ala and Y is often a Pro
[105].
Screening of bioactive peptides derived from proteolytic
degradation of a parent protein is a relatively new field of
research and some peptides derived from collagen of skin
and tendons have been found to possess ACE inhibitory ac-
tivity [105]. Many peptides isolated from skin hydrolysates
of marine organisms like squid, pacific cod, black tip shark
gelatin, sea cucumber and thornback ray have been shown to
possess A CE inhibitory activity (Table 3). Collagen hydro-
lysates are obtained after digestion with different enzymes
like pepsin, flavorzyme, papain, trypsin, alcalase, pancreatin
and ACE inhibitory peptides have been isolated from them
Fig. (1). Regulation of peptide bioactivity - stepwise action of proteases of different specificity.
4 Protein & Peptide Letters, 2016, Vol. 23, No. 7 Banerjee and Shanthi
Table 1. Cryptic Regions in Collagen Types.
Collagen type IV 1(arresten)
2 (Canstatin)
3 (Tumstatin)
4 (tetrastatin)
5 (pentastatin)
6 (hexastatin)
Anti-angiogenic, tumor growth inhibition
Anti-angiogenic, tumor growth inhibition, apoptotic
Anti-angiogenic, tumor growth & protein synthesis inhi-
bition
Anti-tumorogenic
Anti-angiogenic
Anti-angiogenic
Colorado, P.C.et al. (2000) [70]
Kamphaus, G.D. et al. (2000) [71]
Maeshima, Y. et al. (2000) [69]
[47] [48] [49]
Brassart Pasco et al. (2012) [72]
Koskimaki,J.E et al. (2010)[73]
Karagiannis,E.D. et al. (2007);
Akulapalli,S. et al.(2011) [74,75]
Collagen type XV 1 (Restin) Anti-angiogenic, tumor growth inhibition Ramchandran, R. et al. (1999) [68]
Collagen type XVIII
(Endostatin)
Anti-angiogenic, tumor growth inhibition, apoptotic O’Reilly, M.S. et al. (1997) [67]
Dhanabal, M et al. (1999) [76]
Collagen types I, II, III Chemotactic activity Postlethwaite, A .E.et al (1985) [77]
Collagen (placental) Anti-oxidative property Togashi, S. et al. (2002) [78]
Table 2. Antioxidative Peptides from Collagen.
Source Protease Characteristics of Peptide Reference
Collagen type I bovine tendon
Protease from Alcaligenes sp GETBPAGPAG-
PIGPVGARGPAGPQGPRGDKGDTGD
Q
Banerjee. P. et al (2012) [64]
Porcine Skin collagen Protease from Streptomyces and
Bacillus
DGAR Li,B. et al (2007) [85]
Marine fish and bovine skin Alcalase Gly-Pro-Hyp and HGPLGPL Kim,S.K. et al. (2001) [86]
Human placenta Clostridium histolyticum
collagenase
MW 25 to 43 kDa Togashi,S.I. et al. (2002) [73]
Fish scale collagen Chemical hydrolysis MW 500 to 1000 kDa Azuma,K. et al. (2014) [93]
Jelly fish collagen Trypsin and properase E MW 400 to 1200 Da Zhuang,Y. et al. (2009) [94]
Bullfrog skin Alcalase LEELEEELEGCE Zhog-Ji-Qian et al (2008) [91]
Tuna backbone Pepsin VLAGFAYTANQQLS Je,J.Y. et al. (2007)[92]
Squid and sole gelatins Alcalase MW below 30 kDa Giménez,B. et al. (2009) [95]
Giant catfish skin Porcine trypsin MW 7 to 0.1 kDa Ketnawa, S. et al. (2016) [96]
Alaska Pollack skin Mackerel intestine crude enzyme LPHSGY Je,J.Y et al (2005)[97]
Jumbo squid skin gelatin Trypsin FDSGPAGVL and NGPLQAGDRA E Mendis et al (2005)[98]
Nile tilapia scale gelatin Alcalase DPALATEPDPMPF Ngo,D.H. et al (2010) [99]
Cobia gelatin Pancreatin Mixture of peptides with MW <3 kDa Yang J I. (2008) [100]
Thornback ray skin Enzyme preparation from Bacillus
subtilis A26
Mixture of peptides 400 to 2000 Da Lassoued, I. et al. (2015) [101]
Cryptic Peptides from Collagen - A Critical Review Protein & Peptide Letters, 2016, Vol. 23, No. 7 5
[107]. Lafarge et al performed in silico analysis for predic-
tion of bioactive peptides in collagen, chemically synthesiz-
ing the same and studied their ACE inhibitory properties
[108]. Zhuang et al studied the ACE inhibitory efficacy of
peptides from jelly fish collagen. Jelly fish co llagen was
cleaved with six different proteases and the hydrolysate con-
ditions were optimized using response surface methodology
[109]. Purification of the hydrolysate using ion exchange, gel
filtration and ultrafiltration membrane resulted in peptides of
molecular weight range from 200 to 600 Da possessing ACE
inhibitory property. Two ACE inhibitory peptides D1 and E2
(sequence mentioned in Table 3) were isolated from Achilles
tendon digested using crude protease from Alcaligenes sp.
and both possess a common sequence GAXG which proba-
bly imparts bioactivity [105]. Unlike other ACE inhibitory
peptides, D1 and E2 arre larger in size implicating a struc-
tural role for the rest of the sequence.
2.7. Cell Adhesive and Wound Healing Peptides
Cell adhesion is a complex process that plays a major
role in the development of multicellular organisms. It con-
sists of two major steps: the interaction of the ECM binding
site with the cell adhesion receptor protein leading to cell
attachment followed by remod eling of the cytoskeletal fila-
ments supporting the cell shape and spreading of the cell on
the substratum [93,115,116].
The interaction between type I collagen and cells is fa-
cilitated by integrins, a large family of cell-ECM adhesion
receptors involved in anchorage and bidirectional signal
transfer (Fig. 2). Binding initiates the formation of protein
aggregates, termed focal adhesions sites that link integrins to
the cytoskeletons as well as to a cascade of other cellular
events involved in development, growth, apoptosis and re-
sponse of cells to stress signals. In response to changes in the
ECM, integrin signaling also regulates many other interre-
lated cellular processes: proliferation, survival, cell migra-
tion and invasion [117]. Adhesion-dependent survival is a
fundamental aspect of cell behavior. Normal healthy cells
receive pro-survival cues from the ECM. Certain sites in
ECM proteins that have been identified to have a probable
role in cell adhesion are subjects of serious discussions. The
amino acid sequence DGEA present in collagen serves as a
recognition site for the 2 1 integrin complex on platelets
and other cells [117]. Cyanogen treated collagen peptides
improved adhesive behavior in rat hepatocytes [118]. Two
cryptic peptides C2 (2.8 kDa) and E1 (3.2 kDa) have been
identified in collagen type I chain displaying cell activity
regulatory properties [116, 119]. The peptide C2 exhibits cell
adhesion properties (sequence: GPOGPOGKNGDDGEA
GKPGRPG) and the RGD-containing peptide E1 (sequence:
GETGPAGPAGPIGPVGARGPAGPQGPRGDKGETGEQ)
exhibits both cell adhesive and anti-oxidative properties.
Using bioinformatics tools, small sequences have been iden-
tified in C2 which are the probable regions that promote cell
adhesion [119]. E1 and C2 have also been found to combat
stress and wound healing property in Vero cells [116].
Cell proliferation and migration play a vital role in
wound healing. Both migration and proliferation of keratino-
cytes are required for re-epithelialization during wound-
healing, and this process is mediated by growth factors, cy-
tokines, and components of the extracellular matrix [120,
121]. Studies on pepsin soluble collagen from red cucumber
have proved its wound healing role through induction of
fibronectin synthesis [122]. Peptides cleaved from bovine
Achilles tendon have good wound healing property [123]
and improve wound healing under stress [116]. Wound heal-
ing involves a complex hierarchy of chemical stimulations
and their physiological effects on cells. During collagen re-
modeling upon stress or in skin wound healing, the incoming
fibroblasts degrade the basal collagen leading to release of
several cryptic peptides, which act as physiological modula-
tors.
3. ADVANTAGES OF COLLAGEN PEPTIDES FOR
THERAPEUTICAL APPLICATIONS
Collagen peptides display certain advantages over other
therapeutic peptides:
Fig. (2). ECM signaling through integrin receptors to modulate cellular activity.
6 Protein & Peptide Letters, 2016, Vol. 23, No. 7 Banerjee and Shanthi
(i) Stability/ bioavailability: Chymotrypsin, trypsin and
elastase are three major digestive enzymes responsible
for breakdown of ingested proteins and peptides. All of
these enzymes have an active serine and a catalytically
important histidine residue in their active sites. Chymo-
trypsin cleaves after positively charged residues, Arg
and Lys, trypsin cleaves after Phe, Trp and Tyr while
elastase cleaves after Gly, Ser and Val. The choice of
the scissile bond is dependent on the specific ‘pockets’
in these enzymes that are specific for certain types of
residues. However, the enzymes have a constraint; pres-
ence of a Pro residue after the scissile bond renders the
proteases unable to cleave the bond. A similar constraint
is also observed with pepsin, which cleaves after Lys,
Phe, Trp and Tyr at an acidic pH, but does not if the
residues are followed by Pro. The presence of excess
Pro in collagen peptides (10-30% abundance) in com-
parison to other bioactive peptides allows increased
bioavailability of peptides [119]. Collagen peptides do
not contain mentionable amounts of Tyr, Trp and Phe
residues, with the common amino acids recognized by
digestive proteases. The unique amino acid content and
structure of collagen render it with lesser quantity of
protease cleavage sites, thus conferring resistance
against the commonly occurring proteases. However,
continuous protease exposure leads to less efficient
cleavage in other unspecific cleavage sites.
(ii) Biocompatibility: Sequence and structure of collagen
from different sources are nearly identical in the animal
kingdom and this ensures a low immunogenicity of col-
lagen peptides applied in vivo. Human and bovine colla-
gen type I chains have 97% identical sequences and
thus peptides from bovine collagen can be safely used as
therapeutic agents [124,125].
(iii) Collagen is one of the most abundant proteins on Earth;
it is inexpensive and widely available [123] so much so
that even meat industry waste can be used as inexpen-
sive collagen source [126]. Isolation of cryptic regions
from such an inexpensive source would lead to a high
benefit-to-cost ratio. Moreover, such an approach can
help in deriving value from slaughterhouse waste.
CONCLUSION
The realm of cryptic peptide unmasking, activity and
termination may seem very complicated but active research
in the area has come out with ample evidence that there ex-
ists a definite relationship between structure and bioactivities
of cryptic peptides. The growing number of recorded bioac-
tive cryptic peptides suggests that they may be a part of a
general strategy adopted during evolution to serve as a sec-
ondary layer of activity hidden inside a primary layer, to be
exposed only when required. Such a natural phenomenon if
understood well in terms of composition and sequence of
amino acids in the cryptic peptides can lead to very useful,
safer and effective biomedical applications. Collagen bein g
abundantly available protein in nature, can be an ideal and
yet an inexpensive source for isolation of cryptic peptides for
many therap eutic applications.
ABBREVIATIONS
ECM = Extracellular matrix
MMP = Matrix metallo proteinases
ACE = Angiotensin Converting Enzyme
MW = molecular weight
Table 3. ACE Inhibitory Peptides of Collagen from Various Sources.
Source Protease used for hy-
drolysis
Characteristics of Peptide Reference
Squid gelatin hydrolysate Alcalase MW 1400 to 500 Da Aleman, A. et al. (2011) [110]
Sea cucumber gelatin hydrolysate Bromelain and alcalase MW <1kDa Zhao, Y. et al. (2007) [111]
Thornback ray gelatin hydrolysate Crude alkaline protease
from R clavata
SPGPMGPR Lassoued, I. et al. (2015) [87]
Thorn ray gelatin hydrolysate Alcalase GFPGPDGPPGPR Lassoued, I. et al. (2015) [87]
Bovine tendon Crude protease from Alca-
ligenes sps
AKGANGAP-
GIAGAPGFPGARGPSGPQGPSGPP (D1)
PAGNPGADGQPGAKGANGAP (E2)
Banerjee, P. et al. (2012) [105]
Sea bream scales Alkaline protease Gly-Tyr, Val-Tyr, Gly-Phe and Val-Ile-Tyr Fahmi, A. et al. (2004) [112]
Chicken leg
Hydrolysate
Aspergillus sp derived
enzyme
GAOGLOGP Saiga, A. et al. (2008) [113]
Atlantic salmon skin Alcalase and papain Ala-Pro and Val-Arg Gu, R.Z. et al. (2011) [114]
Jellyfish Alcalase MW 200 to 600 Da Zhuang, Y. et al. (2010) [109]
Porcine skin Protease GFOGP Ichimura, T. et al. (2009) [34]
Cryptic Peptides from Collagen - A Critical Review Protein & Peptide Letters, 2016, Vol. 23, No. 7 7
CONFLICT OF INTEREST
The authors do not have any conflict of interest.
ACKNOWLEDGEMENTS
This study was partly supported by research grant form
DST, Govt of India and VIT University.
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