13122-91-3

Usage

Chemical Properties

White to off-white powder

Uses

Substrate for cathepsin A.

InChI:InChI=1/C26H26N2O5/c29-24(27-23(25(30)31)17-20-12-6-2-7-13-20)22(16-19-10-4-1-5-11-19)28-26(32)33-18-21-14-8-3-9-15-21/h1-15,22-23H,16-18H2,(H,27,29)(H,28,32)(H,30,31)/t22-,23-/m0/s1

Upstream product

• 4892-10-8 N-(benzyloxycarbonyl)-L-phenylalanyl-L-phenylalanine methyl ester 
• 63-91-2 L-phenylalanine 
• 17543-49-6 (S)-benzyloxycarbonylphenylalanine pentafluorophenyl ester 
• 10466-61-2 (2S)-amino-4-methylpentanamide hydrochloride 
• 769922-77-2 (S)-benzyl (1-(1H-benzo[d][1,2,3]triazol-1-yl)-1-oxo-3-phenylpropan-2-yl)carbamate 
• 1161-13-3 N-Cbz-L-Phe 
• 501-53-1 benzyl chloroformate 
• 126028-14-6 2,2,2-trifluoroethyl ((benzyloxy)carbonyl)-L-phenylalaninate 
• 3397-32-8 N-(benzyloxycarbonyl)-phenylalanine-N-hydroxysuccinimide ester 
• 117999-34-5 Z-ΔPhe-(R)-Phe-OH 
• 117999-31-2 Z-ΔPhe-(S)-Phe-OH 
• 41518-17-6 Z-Phe-O-COO-isoBu 
• 109453-49-8 (C₈H₇O₂)(NHCHCOO)(CH₂C₆H₅)(CO₂C₂H₅) 
• 2577-90-4 methyl (2S)-2-amino-3-phenylpropanoate 

Downstream Products

• 91841-74-6 Boc-Phe-Phe-OPet 
• 77738-72-8 (S)-1-[(S)-2-((S)-2-Benzyloxycarbonylamino-3-phenyl-propionylamino)-3-phenyl-propionyl]-pyrrolidine-2-carboxylic acid 4-nitro-phenyl ester 
• 2577-41-5 (S)-benzyl 2-((S)-2-(((benzyloxy)carbonyl)amino)-3-phenylpropanamido)-3-phenylpropanoate 
• 115572-55-9 1-[(S)-2-((S)-2-Amino-3-phenyl-propionylamino)-3-phenyl-propionylamino]-cyclopentanecarboxylic acid ethyl ester 
• 141056-54-4 N-benzyloxycarbonyl-L-phenylalanyl-L-phenylalaninamide 
• 183609-76-9 methyl (R)-1-{(S)-2-[(S)-2-amino-3-phenylpropanamido]-3-phenylpropanoyl}pyrrolidine-2-carboxylate 

Relevant academic research and scientific papers

Effects of normal and their branched alcohols with structurally minimal variation on kinetic parameters in thermolysin-catalyzed peptide hydrolysis and synthesis of N-(benzyloxycarbonyl)-L-phenylalanyl-L-phenylalanine and its methyl ester.

When higher alcoholic solvents were added to the reaction medium, and the enhancement of the enzyme activity, followed by its reduction then inactivation, were observed in thermolysin-catalyzed peptide hydrolysis and synthesis. The organic solvent content used was less than the saturating concentration in the buffer (i.e., water-organic one-phase system). The kinetic parameters, Km and kcat, at the alcoholic concentration giving maximal enzyme activity in these reactions changed linearly with increasing logP values of the alcohols and consequently kcat/Km as well. When the branched isomers of alcohols with structurally minimal variation of which logP was equivalent theoretically, were used as annexments, the kinetic parameters were also changed. The results, especially the changes of Km for each organic solvent, suggested that each alcohol should act at the active site of the enzyme in its own effective mode.

Design and synthesis of novel hydroxypyridinone derivatives as potential tyrosinase inhibitors

Two groups of novel hydroxypyridinone derivatives 6(a-e) and 12(a-c), were designed as potential tyrosinase inhibitors, and synthesized using kojic acid as a starting material. The tyrosinase inhibitory activity of these two groups was demonstrated to be potent, especially compounds 6e and 12a, whose IC50 values for monophenolase activity were 1.95 μM and 2.79 μM, respectively. Both of these values are lower than that of kojic acid (IC50 = 12.50 μM). Compounds 6e and 12a were investigated for the inhibitory effect on diphenolase activity. The results showed that the inhibitory mechanism of these two compounds was reversible and that the inhibitory type was a competitive-uncompetitive mixed-type. The values of IC50 of 6e and 12a on the diphenolase activity of tyrosinase were determined to be 8.97 μM and 26.20 μM, respectively. The inhibitory constants (KI and KIS) of 6e were determined as 17.17 μM and 22.09 μM, respectively; and the KI and KIS values of 12a were 34.41 μM and 79.02 μM, respectively. Compound 6e showed a greater ability to reduce copper and a stronger copper chelating ability than kojic acid.

Extraordinary Diastereoselectivity Coupled to Altered Structure of Dipeptide Esters

The diastereoselectivity for the hydrolysis of Z-D(L)-Phe-L-Phe p-methoxycarbonylphenyl ester was maximized (ksDL/ksLL=34) at the optimum temperature (30 deg C).This could be attributed to the conformational change in the DL isomer, which was supported by the circular dichroism measurements.

A catalytic one-step synthesis of peptide thioacids: the synthesis of leuprorelin via iterative peptide-fragment coupling reactions

A catalytic one-step synthesis of peptide thioacids was developed. The oxygen-sulfur atom exchange reaction converted the carboxy group at the C-terminus of the peptides into a thiocarboxy group with suppressed epimerization. This method was successfully applied to the synthesis of the peptide drug leuprorelin via an iterative fragment-coupling protocol.

Convenient green preparation of dipeptides using unprotected α-amino acids

Dipeptides and amides were obtained in high yields from N-carbobenzyloxy α-amino acids and 3-phenylpropanoic acid with unprotected α-amino acids via the corresponding mixed carbonic carboxylic anhydrides using ethyl chloroformate and triethylamine by an ecological and convenient method in which the protection of C-terminals is not needed.

A Modular Synthesis of Some Biologically Relevant Cyclic Peptides through Late-Stage Functionalization

A modular synthesis of some cyclic peptides related to a class of histone deacetylase inhibitors is reported. The synthesis utilizes a late-stage functionalization of a cyclic tetrapeptide scaffold to link the pendant alkyl chain through cross metathesis. It is observed that while the cross-metathesis reaction of a terminal olefin having a β-substituent is marginally successful with the scaffold, the corresponding reaction with an α,β-unsaturated ketone/ester is more promising. The utility of the protocol is demonstrated through the preparation of three cyclic tetrapeptides structurally related to the novel histone deacetylase inhibitors FR-225497 and trapoxin B.

Synthesis, bioactivity, docking and molecular dynamics studies of furan-based peptides as 20s proteasome inhibitors

Proteasome inhibitors are promising compounds for a number of therapies, including cardiovascular and eye diseases, diabetes, and cancers. We previously reported a series of furanbased peptidic inhibitors with moderate potencies against the proteasome b5 subunit, hypothesizing that the C-terminal furyl ketone motif could form a covalent bond with the catalytic residue, threonine 1. In this context, we describe further optimizations of the furan-based peptides, and a series of dipeptidic and tripeptidic inhibitors were designed and synthesized, aiming at improved potency and better solubility. Most of the tripeptidic inhibitors demonstrated improved potency and selectivity as b5 subunit inhibitors in both enzymatic and cellular assays, and good antineoplastic activities in various tumor cell lines were also observed. However, no inhibitory effects were observed for the dipeptidic compounds, which led us to presume that a noncovalent binding mode is adopted. Docking studies and molecular dynamics simulations were carried out to verify this presumption, with results showing that the distance between the furyl ketone motif and Thr1 is slightly too long to form covalent bond.

Mechanistic insight into the lability of the benzyloxycarbonyl (Z) group in N-protected peptides under mild basic conditions

An unexpected lability of the benzyloxycarbonyl (Z) protecting group under mild basic conditions at room temperature is explained by a mechanism based on anchimeric assistance. It is found that the vicinal amide group stabilises the tetrahedral intermediate formed after nucleophilic addition of hydroxide to the carbonyl of the Z group. This effect operates in N-protected tripeptides and tetrapeptides but Z-protected dipeptides are stable under the same conditions due to blockage of the vicinal amide NH by intramolecular H-bonding with the terminal carboxylate moiety. Copyright

α-N-Protected dipeptide acids: A simple and efficient synthesis via the easily accessible mixed anhydride method using free amino acids in DMSO and tetrabutylammonium hydroxide

The importance of dipeptides both in medicinal and pharmacological fields is well documented and many efforts have been made to find simple and efficient methods for their synthesis. For this reason, we have investigated the synthesis of α-N-protected dipeptide acids by reacting the easily accessible mixed anhydride of α-N-protected amino acids with free amino acids under different reaction conditions. The combination of TBA-OH and DMSO has been found to be the best to overcome the low solubility of amino acids in organic solvents. Under these experimental conditions, the homogeneous phase condensation reaction occurs rapidly and without detectable epimerization. The present method is also applicable to side-chain unprotected Tyr, Trp, Glu, and Asp but not Lys. This latter residue is able to engage two molecules of mixed anhydride giving the corresponding isotripeptide. Moreover, the applicability of this protocol for the synthesis of tri- and tetrapeptides has been tested. This approach reduces the need for protecting groups, is cost effective, scalable, and yields dipeptide acids that can be used as building blocks in the synthesis of larger peptides.

Convenient peptide synthesis without protection of C-Terminals

Condensation of carboxylic acids 1 and 5 with unprotected α-amino acids 2 via activation by ethyl chloroformate and triethylamine proceeded effectively to afford the corresponding amides in 5099% yields. Tripeptide 7c was obtained in 42% yield from the dipeptide 6c in a similar manner.