133463-36-2

Upstream product

• 26048-69-1 (S)-2-tert-Butoxycarbonylamino-succinic acid 4-benzyl ester 1-(4-nitro-phenyl) ester 
• 7517-19-3 methyl (L)-leucinate hydrochloride 
• 7536-58-5 BOC-L-aspartic acid 4-benzyl ester 

Downstream Products

• 118884-45-0 ((S)-4-(benzyloxy)-2-((tert-butoxycarbonyl)amino)-4-oxobutanoyl)-L-leucine 
• 1381946-51-5 cyclo(4-benzyl-L-Asp-L-Leu) 
• 77302-88-6 Boc-Asp(OBzl)-Asp(OBzl)-Leu-OMe 

Relevant academic research and scientific papers

Macrocyclic Inhibitors of HGF-Activating Serine Proteases Overcome Resistance to Receptor Tyrosine Kinase Inhibitors and Block Lung Cancer Progression

Hepatocyte growth factor (HGF), the ligand for the MET receptor tyrosine kinase, is a tumor-promoting factor that is abundant in the tumor microenvironment. Proteolytic activation of inactive pro-HGF by one or more of the serine endopeptidases matriptase, hepsin, and HGF activator is the rate-limiting step in HGF/MET signaling. Herein, we have rationally designed a novel class of side chain cyclized macrocyclic peptide inhibitors. The new series of cyclic tripeptides has superior metabolic stability and significantly improved pharmacokinetics in mice relative to the corresponding linear peptides. We identified the lead compound VD2173 that potently inhibits matriptase and hepsin, which was tested in parallel alongside the acyclic inhibitor ZFH7116 using both in vitro and in vivo models of lung cancer. We demonstrated that both compounds block pro-HGF activation, abrogate HGF-mediated wound healing, and overcome resistance to EGFR- and MET-targeted therapy in lung cancer models. Furthermore, VD2173 inhibited HGF-dependent growth of lung cancer tumors in mice.

Cyclic dipeptides exhibit potency for scavenging radicals

Twenty kinds of cyclic dipeptides containing l-leucine were synthesized, and their antioxidant activity against .OH and O2·- was investigated. Compounds possessing polar amino acid residues, such as Asp, Cys, Glu, Lys, Pro, Ser, and Trp, exhibited higher antioxidant activity against .OH than vitamin E. However, only cyclo(l-Cys-l-Leu) scavenged O2·-.

Synthesis of Peptide Analogues of Prothrombin Precursor Sequence 5-9. Substrate Specificity of Vitamin K Dependent Carboxylase

Thirty-five analogues of Phe-Leu-Glu-Glu-Leu, the pentapeptide sequence 5-9 of bovine prothrombin precursor, were synthesized and assayed as potential substrates or inhibitors of rat liver vitamin K dependent carboxylase.Carboxylation of substrate was determined by measuring the incorporation of carbon-14 labeled bicarbonate into product.Changes in substrate carboxylation produced by changing peptide chain length, amino acid chirality, or the distance seperating the peptide chain backbone from the carboxyl group were measured.The data suggest that the carboxylase carboxylates L-glutamic acid residues and does not carboxylate L-aspartic acid, L-homoglutamic acid, glutamine, or D-glutamic acid residues; tri- through pentapeptides are better substrates than mono- or bis(amino acid) derivatives, and hydrophobic groups added to the N-terminus can produce better substrates for the enzyme.None of the synthetic substrates is carboxylated as effectively as the endogenous protein substrates for the enzyme.The effect of structure on additional parameters affecting carboxylation is discussed.