Studies on the QSAR of ACE Inhibitory Tripeptides with Proline as C-Terminal and Determination Inhibitory Activities

A database of 38 tripeptides with C-terminal proline was constructed to study QSAR of ACE inhibitory peptides. The model was established using PLS based on the three z-scores of 20 coded amino acids. The prediction ability of tripeptides model was improved with proline as terminal. The coefficient of determination(R2) and the cross validated coefficient(Q2LOO) of the model are 0.856 and 0.782 respectively. According to the model, two potential ACE inhibitory tripeptides IIP and IVP were synthesized. Their IC50(inhibitor concentration that reduced enzyme activity by 50%) were proved to be 1.58 and 1.39 μM respectively by direct spectrophotometric measurement, and they are very close to the predicted value by the model.

Synthesis of Cell Adhesive Motif RGD Tripeptide by a Novel Chemical Method and Its Purification

The cell adhesive motif RGD tripeptide was synthesized by using a novel chemical method. First, Gly-Asp（GD） was synthesized in two steps including the chloroacetylation of free L-aspartic acid and the ammonolysis of the chloroacetylated L-aspartic acid. The yield of chloroacetylated L-aspartic acid was 83.0%. For the ammonolysis of chloroacetylated L-aspartic acid, the yield of the ammonolyzed product was 92. 3%. Second, the coupling between Arg and Gly-Asp was carried out by using the NCA method. The maximum yield of RGD was about 50% at 0℃ and pH = 9. 5. The prepared RGD tripeptide was confirmed by using amino acid component analysis and mass spectrographic analysis.

Synthesis and Structure Analysis of a Tripeptide Containing N-methyl Group Amino Acid

A convenient method of synthesizing a tripeptide-containing N-methyl group amino acid was developed using O-benzotriazole-N,N,N＇,N＇-tetramethyluronium-hexafluorophosphate as the condensing agent. The crystals of tripeptide had white needles belonging to the orthorhombic space group P2_12_12_1. The conformational preference for homochiral tripeptides with one N-methylated amide bond was also investigated. Crystal-structure analysis showed that homochiral tripeptides with an internal N-methylated amide bond preferred a trans-amide form, thereby giving the peptide β-fold characteristics. Intermolecular C-H···O and N-H···O hydrogen bonds linked the molecules into a one-dimensional chain and stabilized the structure.

Enzymatic Synthesis of a CCK-8 Tripeptide Derivative

The enzymatic synthesis of CCK-8 tripeptide derivative Phac-Met-Asp(OMe)-Phe-NH2 is reported. Starting with Phac-Met-OCam, we have successfully synthesized the target tripeptide with three free or immobilized enzymes, ?chymotrypsin, papain and thermolysin in reasonable yields. The key steps in this synthesis were the coupling of Phac-Met-OCam and H-Asp(OMe)2 to form Met-Asp peptide bond catalyzed by ?chymotrypsin and the selective hydrolysis of -ester of Phac-Met-Asp(OMe)2 catalyzed by papain.

Tissue-targeting lead generation and optimization from random and directed screening of technetium-99m labeled tripeptide complex libraries in vivo

Background Screening libraries against a molecular target in vitro are idealized models that cannot reflect the real state in vivo where biomolecules coexist and interact. C-terminal amide tripeptides labelled with Technetium-99m can provide a unique noninvasive approach to trace a large number of compounds in vivo. Methods The C-terminal amide tripeptide libraries were synthesized on Rink Amide-MBHA resin using iterative and pooling protocol. Technetium （V） oxo core [TcO^3＋] was bound to each tripeptide via 4 deprotonated nitrogen atoms to form a library of 8000 ^99mTc tripeptoid complexes. The radiocombinatorial screening （RCS） in vivo was carried out on SD rats and A549 tumour bearing mice. Results Signals of tissue distribution and metabolism of libraries were recorded by counting or imaging and tissue targeting leads identified by both random and directed RCS. Among them, ^99mTc RPA, ^99mTc VIG and ^99mTC RES had specific tissue targeting in kidney, liver and tumour respectively. The percent injected dose per gram tissue of ^99mTc labelled leads in their target tissue was highly structure dependent. Because the nontarget tissue binding and the metabolism of ^99mTc tripeptoid sublibraries were simultaneously monitored successfully by RCS, the interference of background activity was limited to the lowest level. Optimization of renal function agent from the labelled libraries was carried out by directed screening. ^99mTc DSG was finally identified the most promising agent for renal function studies. Conclusions RCS in vivo is a powerful tool for the discovery of tissue targeting drugs. The potential screening bias is probably the major limitation of labelled libraries.

Self-assembled fluorescent tripeptide nanoparticles for bioimaging and drug delivery applications

Peptide self-assembled nanomaterials have attracted more and more attention due to their wide applications such as drug delive ry,cell imaging,and real-time drug monitoring.However,the application of the peptide is still limited by its inherent optical properties.Here we proposed and prepared a series of fluorescent tripeptide nanoparticles(TPNPs)through π-π stacking and zinc coordination.The experimental results show that the nanoparticles(TPNPs1)formed by the self-assembly of the tripeptide tryptophan-tryptophan-tryptophan have the highest fluorescence intensity,uniform and appropriate size,and low cytotoxicity.Furthermore,there was fluorescence resonance between TPNPs1 and doxorubicin,which has been successfully applied for real-time cell imaging and drug release monitoring.

Enzymatic Synthesis of a CCK-8 Tripeptide Fragment

A process for the synthesis of CCK-8 tripeptide H-Gly-Trp-Met-OH catalyzed by immobilized enzyme was re-ported. Enzymes were used for the formation of peptide bonds and the removal of protecting group. Starting with phenylacetyl (PhAc) glycin, N-protected dipeptide PhAc-Gly-Trp-OMe was obtained by coupling PhAc-protected glycine carboxamidomethyl ester (OCam) with Trp-OMe catalyzed by immobilized papain in buffered ethyl acetate. Then the condensation between PhAc-Gly-Trp-OMe and Met-OEtHCl was carried out by immobilized -chy-motrypsin catalysis in solvent free system. Basic hydrolysis was followed getting PhAc-Gly-Trp-Met-OH. The PhAc-group was removed with penicillin G amidase and H-Gly-Trp-Met-OH was obtained in an overall yield of 43.9%. The reaction conversion of tripeptide in solvent free system was strongly affected by the system of basic salts added. The influence of the support materials used to deposit enzymes and structures of acyl donor and nu-cleophile on the reaction was also investigated.

Dock-able linear and homodetic di, tri, tetra and pentapeptide library from canonical amino acids: SARS-CoV-2 Mpro as a case study

Peptide-based therapeutics are increasingly pushing to the forefront of biomedicine with their promise of high specificity and low toxicity.Although noncanonical residues can always be used,employing only the natural 20 residues restricts the chemical space to a finite dimension allowing for comprehensive in silico screening.Towards this goal,the dataset comprising all possible di-,tri-,and tetra-peptide combinations of the canonical residues has been previously reported.However,with increasing computational power,the comprehensive set of pentapeptides is now also feasible for screening as the comprehensive set of cyclic peptides comprising four or five residues.Here,we provide both the complete and prefiltered libraries of all di-,tri-,tetra-,and penta-peptide sequences from 20 canonical amino acids and their homodetic(N-to-C-terminal)cyclic homologues.The FASTA,simplified molecular-input line-entry system(SMILES),and structure-data file(SDF)-three dimension(3D)libraries can be readily used for screening against protein targets.We also provide a simple method and tool for conducting identity-based filtering.Access to this dataset will accelerate small peptide screening workflows and encourage their use in drug discovery campaigns.As a case study,the developed library was screened against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)main protease to identify potential small peptide inhibitors.

Peptide-based enteral formula improves tolerance and clinical outcomes in abdominal surgery patients relative to a whole protein enteral formula

AIM To compare a dipeptide- and tripeptide-based enteral formula with a standard enteral formula for tolerance and nutritional outcomes in abdominal surgery patients.METHODS A retrospective study was performed to assess the differences between a whole-protein formula(WPF) and a dipeptide- and tripeptide-based formula(PEF) in clinical outcomes.Seventy-two adult intensive care unit(ICU) patients with serum albumin concentrations less than 3.0 g/d L were enrolled in this study.Patients were divided into two groups(WPF group = 40 patients,PEF group = 32 patients).The study patients were fed for at least 7 d,with ≥ 1000 m L of enteral formula infused on at least 3 of the days.RESULTS The mean serum albumin level on postoperative day(POD) 10,prealbumin levels on POD-5 and POD-10,and total lymphocyte count on POD-5 were significantly higher in the PEF group compared to those in the WPF group(P < 0.05).The average maximum gastric residual volume of the PEF patients during their ICU stays was significantly lower than that for WPF patients.CONCLUSION Dipeptide- and tripeptide-based enteral formulas are more efficacious and better tolerated than wholeprotein formulas.

Synthesis and DNA Cleavage Studies of 2,6-Dimethoxyhydroquinone-3-Mercaptoacetic Acid Conjugates

In an effort to investigate the use of short peptide chains as carriers of new anti-tumor agents, we synthesized four tripeptide-cytotoxic agent conjugates: DMQ-MA-Lys(DMQ-MA)-Phe -Arg-Ome, DMQ-MA-Lys(DMQ-MA)-Ile-Arg-Ome, DMQ-MA-Lys(DMQ-MA)-Val-Arg-Ome, DMQ-MA-Lys(DMQ-MA)-Lys(Cbz)-Arg-Ome. The cytotoxic agent conjugated to the N-terminal and the xi -amino group of Lysine of the tripeptide is 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA). The tripeptides were synthesized by coupling protected amino acid residues according to Pfp/DCC methods (Pfp: pentafluorophenol, DCC:N,N'-dicyclohexyl-carbodiimide) in solution. Agarose gel electrophoresis showed that these compounds can cleave supercoiled DNA into open-circular form in drug concentration as low as 4-50 mu M without H2O2 and UV irradiation. Further studies on their cytotoxicity for these conjugates are ongoing.