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Solid-phase peptide synthesis. (A) Structure of Rink Amide AM Resin. (B) Attaching first amino acid (Ser) and peptide chain elongation by cycles of deprotection and coupling steps. Fmoc 9-Fluorenylmethoxycarbonyl, tBu tert-butyl, Boc tert-butyloxycarbonyl, PyBOP benzotriazol-1-yloxytri(pyrrolidino) phosphonium hexafluorophosphate, HBTU 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethylaminium hexafluorophosphate, HOBt 1-hydroxybenzotriazole
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Synthesis of artificial antibacterial peptides containing multiple disulfide bridges is of particular interest in bioorganic chemistry. In this paper, a straightforward on-resin synthesis of a cyclic peptide containing two disulfide bridges by orthogonal protection approach is presented. This artificial peptide is a biomimetic peptide that has stru...
Citations
... The formation of disulfide bonds entails the deprotection of cysteine residues to expose free sulfhydryl groups, which are subsequently oxidized to form the disulfide bond. Both deprotection and oxidation steps can occur sequentially or simultaneously [24]. A range of oxidizing reagents can be employed to facilitate the formation of disulfide bonds. ...
Peptides exhibit significant specificity and effective interaction with therapeutic targets, positioning themselves as key players in the global pharmaceutical market. They offer potential treatments for a wide range of diseases, including those that pose significant challenges. Notably, trofinetide (Daybue) peptide marked a groundbreaking achievement by providing the first-ever cure for Rett syndrome, and several peptides have secured FDA approval as first-in-class medications. Furthermore, peptides are expanding their presence in areas traditionally dominated by either small or large molecules. A noteworthy example is the FDA approval of motixafortide (Aphexda) as the first peptide-based chemokine antagonist.
Here, the focus will be on the analysis of FDA-approved peptides, particularly those targeting cardiovascular diseases, human immunodeficiency, the central nervous system, and various other intriguing classes addressing conditions such as osteoporosis, thrombocytopenia, Cushing’s disease, hypoglycemia, among others. The review will explore into the chemical structure of peptides, their indications and modes of action, the developmental trajectory, and potential adverse effects.
... Bicyclic peptides, with dual conformational constraints and rigid structures, are more resistant to proteolytic degradation as compared to linear and monocyclic peptides (Ahangarzadeh et al., 2019). Jaradat et al. (2019) synthesised a cyclopeptide containing two disulphide bonds on a resin by orthogonal protection approach, and the cyclopeptide was analysed and characterised by LC-MS/MS and HPLC. The purified peptide showed excellent antimicrobial activity against the tested Gram-positive and Gram-negative bacteria. ...
Antimicrobial peptides (AMPs) are active short peptides that exist in microorganisms, insects, amphibians, plants, and mammals. Some naturally occurring AMPs have low antimicrobial activity, high haemolysis, potential toxicity toward mammalian cells, and high susceptibility to proteolytic degradation, which limit their practical application. In recent years, many efforts have been made to design and modify AMPs to improve their properties. The present review focuses on site-directed mutation, truncation, hybridisation, capping, and cyclisation of AMPs. The review further introduces the application of solid-phase peptide synthesis technology for AMPs, and summarises the methods for evaluating the antimicrobial activity of AMPs. The in-depth research on AMPs is expected to play an essential role in the fields of agriculture, animal husbandry, food industry, and medicine.
... Therefore, countless studies have been carried out to gain insights into the mechanisms and principles underlying the structural and functional characteristics of biologically active proteins and peptides, which can ultimately be utilized for applications in the medicinal and pharmaceutical industries. 5,6 Such scientific studies require the availability of pure peptides and proteins in reasonable amounts with purity. In this regard, significant research efforts have pursued such access. ...
Peptides are gaining ground in the pharmaceutical arena, with a total of 22 approvals over the last six years. These molecules are also present in antibody-drug conjugate constructs as linkers or payloads, or both. Solid-phase peptide synthesis (SPPS) is the method of choice for peptide synthesis. The introduction of the automatic synthesizer has facilitated this methodology and helped reduce the amounts of solvents needed. However, there are still concerns regarding the amounts, as well as the safety profiles, of the solvents involved in SPPS. Here we discuss work addressing the use of water as the greenest alternative to the common non-green solvents employed in various steps of the SPPS methodology. Various technologies were introduced which enabled the synthesis in aqueous media of di- and up to decapeptide with satisfactory yields and purities.
... An Agilent 1200 -API 4000 LC-MS/MS system was used for recording mass spectra. A preparative Knauer HPLC system was used for peptide purification using a Phenomenex C18 column (250 x 21.2 mm,10 μm) (Jaradat et al., 2019). ...
Increasing antibiotic resistance in Gram-negative bacteria has mandated the development of both novel antibiotics and alternative therapeutic strategies. Evidence of interplay between several gastrointestinal peptides and the gut microbiota led us to investigate potential and broad-spectrum roles for the incretin hormone, human glucose-dependent insulinotropic polypeptide (GIP) against the Enterobacteriaceae bacteria, Escherichia coli and Erwinia amylovora. GIP had a potent disruptive action on drug efflux pumps of the multidrug resistant bacteria E. coli TG1 and E. amylovora 1189 strains. The effect was comparable to bacterial mutants lacking the inner and outer membrane efflux pump factor proteins AcrB and TolC. While GIP was devoid of direct antimicrobial activity, it has a potent membrane depolarizing effect, and at low concentrations, it significantly potentiated the activity of eight antibiotics and bile salt by reducing MICs by 4-8-fold in E. coli TG1 and 4-20-fold in E. amylovora 1189. GIP can thus be regarded as an antimicrobial adjuvant with potential for augmenting the available antibiotic arsenal.
... Accordingly, the present study aims to stabilize GLP-1 in vivo by prolonging its t 1/2 , in which a glucagon-like peptide 1-albumin conjugate can be an ideal tool. We considered employing an additional DTNP modified cysteine residue at the C-terminal of the modified GLP-1, which formed the inter-disulfide bond with another cysteine residue within the HSA (Jaradat et al. 2019;Postma and Albericio 2014). The resultant GLP-1-albumin is presumed to retain the effects of GLP-1, yet exhibits a more prolonged duration in vivo. ...
The rapid degradation of native glucagon-like peptide 1 (GLP-1) by dipeptidyl peptidase-IV (DPP-IV) has advanced new approaches to the generation of degradation-resistant GLP-1 analogs. Chemical coupling of GLP-1 analog to HSA is innovatively achieved by solid-phase peptide synthesis in this study and shows prolonged glucose-lowering ability in vivo. GLP-1(7–37)(Ala8Aib)-Cys-HSA was constructed by solid-phase peptide synthesis through two levels of modification: mutation of Ala8 to aminoisobutyric acid (Aib) to decrease DPP-IV degradation, and conjugation to large serum protein HSA by chemical modification to decrease renal filtration. Glucose tolerance test and insulin secretion assay were performed to examine the biological activity of GLP-1(7–37)(Ala8Aib)-Cys-HSA in vivo in the present research. Long-lasting glucose-lowering and insulin-releasing effects were evaluated up to 4 weeks in T2DM rats. GLP-1(7–37)(Ala8Aib)-Cys-HSA lowered blood glucose in normal mice and T2DM rats. Twice administration of GLP-1(7–37)(Ala8Aib)-Cys-HSA to T2DM rats daily significantly reduced glycemic excursion following IP glucose challenge (P < 0.01 to 0.05) and greatly increased insulin secretion during the 4-week study period. These findings demonstrate that the albumin-conjugated GLP-1 analog mimics the function of native GLP-1 with prolonged activity.
... Numerous studies indicated that the majority of the antioxidant activity may be attributed to anthocyanin, flavones, flavonoids, isoflavones, catechin and other phenolics (Kahkonen et al., 1999) that were found in the tissues of plants (Loliger, 1991;Abu-Romman et al., 2015;Haddad et. al., 2016a, Haddad et al., 2016b, Jaradat et al., 2018. Crops which have high antioxidant activity can serve as an excellent dietary source to improve health (Narwal et al., 2015;Al-Qudah et al., 2016). ...
A field experiment was conducted at the National Center for Agricultural Research and Extension in the Jordan Valley, during summer 2015 to evaluate the effect of cattle manure on antioxidant activity of maize leaves. The study also measured the effect of cattle manure on the bioavailability of heavy metals in maize leaves at harvest. Six treatments were compared, no cattle manure (T1, control), and 4 tons ha ⁻¹ (T2), 8 tons ha ⁻¹ (T3), 12 tons ha ⁻¹ (T4), 16 tons ha ⁻¹ (T5), and 20 tons ha ⁻¹ (T6) cattle manure. ANOVA followed by LSD test were used to compare the treatments at the 5% significance level. Antioxidant activity using DPPH and ABTS were measured for the six leaves extracts representing six treatments of organic manure. A wet digestion method was used to extract the heavy metals from the dry leaf powder samples using atomic absorption spectroscopy. Antioxidant activity for leaves increased significantly with increasing cattle manure amount applied to soil according to DPPH and ABTS radical scavenging activity. The highest antioxidant activity was reached at the highest amount of cattle manure while the control had the lowest. Concentrations of Ni, Cu, Mn, Zn, Cr and Fe contents in maize leaves of plants grown in soil amended with cattle manure were higher compared to plants grown in no-amended soil. Cattle manure amended soil increased Ca, K and P concentrations in the seeds and leaves of maize. The cattle manure was able to encourage a raise on mineral buildup in aerial parts of tested plants.
... Numerous studies indicated that the majority of the antioxidant activity may be attributed to anthocyanin, flavones, flavonoids, isoflavones, catechin and other phenolics (Kahkonen et al., 1999) that were found in the tissues of plants (Loliger, 1991;Abu-Romman et al., 2015;Haddad et. al., 2016a, Haddad et al., 2016b, Jaradat et al., 2018. Crops which have high antioxidant activity can serve as an excellent dietary source to improve health (Narwal et al., 2015;Al-Qudah et al., 2016). ...
A field experiment was conducted at the National Center for Agricultural Research and Extension in the Jordan Valley, during summer 2015 to evaluate the effect of cattle manure on antioxidant activity of maize leaves. The study also measured the effect of cattle manure on the bioavailability of heavy metals in maize leaves at harvest. Six treatments were compared, no cattle manure (T1, control), and 4 tons ha −1 (T2), 8 tons ha −1 (T3), 12 tons ha −1 (T4), 16 tons ha −1 (T5), and 20 tons ha −1 (T6) cattle manure. ANOVA followed by LSD test were used to compare the treatments at the 5% significance level. Antioxidant activity using DPPH and ABTS were measured for the six leaves extracts representing six treatments of organic manure. A wet digestion method was used to extract the heavy metals from t he dry leaf powder samples using atomic absorption spectroscopy. Antioxidant activity for leaves increased significantly with increasing cattle manure amount applied to soil according to DPPH and ABTS radical scavenging activity. The highest antioxidant activity was reached at the highest amount of cattle manure while the control had the lowest. Concentrations of Ni, Cu, M n, Zn, Cr and Fe contents in maize leaves of plants grown in soil amended with cattle manure were higher compared to plants grown in no-amended soil. Cattle manure amended soil increased Ca, K and P concentrations in the seeds and leaves of maize. The cattle manure was able to encourage a raise on mineral buildup in aerial parts of tested plants.
Solid-phase peptide synthesis (SPPS) is the method of choice that enables the access to a library of synthetic bioactive peptides. Cyclization due to the presence of disulfide bridges is of great importance for certain proteins and peptides since it increases their stability against proteolysis by constraining the conformations of these peptides and proteins. Here we describe the solid-phase peptide cyclization by on-resin strategy represented in the synthesis of peptides containing two disulfide bridges. The presence and/or the absence of free SH groups can be investigated by Ellman’s test.
New methodologies for the construction of full peptide structures with all disulfide bonds on the resin are attractive for the development of solid phase peptide synthesis. Detailed reaction conditions for the on‐resin disulfide bond formation have been investigated using a mild and chemically stable oxidizing reagent, methyl 3‐nitro‐2‐pyridinesulfenate (Npys‐OMe). Monocyclic oxytocin, MCH and bicyclic α‐conotoxin ImI were synthesized in both semi‐automated and full‐automated protocols. It was found that on‐resin intramolecular disulfide bond formation with Npys‐OMe proceeds with the minimal formation of peptide oligomers by adopting a solvent system with 0.4 M LiCl/DMF. Crude peptides with complete disulfide bond patterns can be obtained in high purity using both protocols. This minimized the RP‐HPLC purification step and the desired peptides were obtained with better yields. To our knowledge, this is the first fully automated construction of a bicyclic disulfide peptide on resin with more than 50 % purity in Fmoc‐based SPPS. These results suggest that Npys‐OMe is a useful reagent for the disulfide bond formation in automated protocols.
The aim of this study was to investigate levels of vitamin B 12 deficiency in healthy and patient individuals in Petra region in Jordan. The study was designed to include different subject groups based on different factors including gender, age, body mass index (BMI), diet, smoking, and disease (diabetes, hypertension, anemia, and gastrointestinal tract (GIT) problems). 400 participants were enrolled, indeed; (126) healthy (normal), (119) diabetics and (155) hypertension patients. Participants were classified based on age into three groups; (20-39), (40-59), and (60-80) years. Vitamin B 12 levels for hypertensive were significantly Eyad Mallah/ Da'san M. M. Jaradat et al Research Article 1558 IJBPAS, August, 2019, 8(8) higher than those of diabetics for the same group. It was found that vitamin B 12 levels for individuals with good diet, non-smokers, non-anemic and without GIT problems were significantly higher than those of individuals with poor diet, smokers, anemic and GIT problems. In conclusion Vitamin B 12 level is adversely affected by smoking, GIT problems, anemia and poor diet quality.
