114480-07-8

Upstream product

• 42362-08-3 (S)-methyl 2-((S)-2-(((benzyloxy)carbonyl)amino)-3-phenylpropanamido)-6-((tert-butoxycarbonyl)amino)hexanoate 
• 3397-32-8 N-(benzyloxycarbonyl)-phenylalanine-N-hydroxysuccinimide ester 
• 2418-95-3 (S)-2-amino-6-(tert-butoxycarbonylamino)hexanoic acid 
• 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 
• 71989-26-9 Fmoc-Lys(tert-butoxycarbonyl) 
• 2389-48-2 N-ε-tert-butoxycarbonyl-L-lysine methyl ester hydrochloride 

Downstream Products

• 71448-16-3 Cbz-L-Phe-L-Lys-OH 
• 1400743-57-8 (benzyloxycarbonyl)-Phe-Lys-N-ε-(tert-butoxycarbonyl)-(p-aminobenzyl)-OH 
• 1616957-61-9 (benzyloxycarbonyl)-Phe-Lys-N-ε-(tert-butoxycarbonyl)-PABC-(7-amino-4-methylcoumarin) 
• 1616957-45-9 (benzyloxycarbonyl)-Phe-Lys-PABC-(7-amino-4-methylcoumarin)*TFA 
• 1616957-69-7 (benzyloxycarbonyl)-Phe-Lys-PABC-(7-amino-4-methylcoumarin)*HCl 
• 866951-92-0 (S)-3-((S)-2-(((benzyloxy)carbonyl)amino)-3-phenylpropanamido)-7-((tert-butoxycarbonyl)amino)-2-oxoheptyl 2,6-dimethylbenzoate 
• 114480-06-7 Z-Phe-Lys(ε-Boc)CH₂Br 

Relevant academic research and scientific papers

Increasing time on target: utilization of inhibitors of cysteine cathepsins to enhance the tumor retention of receptor-targeted agents

We report a strategy of utilizing irreversible cysteine cathepsin inhibitor as trapping agent to increase the tumor residence time of receptor-targeted agents. The targeted constructs incorporating these cysteine cathepsin trapping agents were able to for

PHOTODYNAMIC QUENCHED ACTIVITY BASED PROBES AND USES THEREOF IN IMAGING AND TARGETED THERAPY

The present invention relates to compounds comprising photosensitizer, compositions comprising the same as well as uses and methods thereof for detection and for treatment using photodynamic therapy.

Prodrug-inspired probes selective to cathepsin B over other cysteine cathepsins

Cathepsin B (CTB) is a cysteine protease believed to be an important therapeutic target or biomarker for several diseases including aggressive cancer, arthritis, and parasitic infections. The development of probes capable of assessing CTB activity in cell lysates, living cells, and animal models of disease are needed to understand its role in disease progression. However, discovering probes selective to cathepsin B over other cysteine cathepsins is a significant challenge due to overlap of preferred substrates and binding site homology in this family of proteases. Herein we report the synthesis and detailed evaluation of two prodrug-inspired fluorogenic peptides designed to be efficient and selective substrate-based probes for CTB. Through cell lysate and cell assays, a promising lead candidate was identified that is efficiently processed and has high specificity for CTB over other cysteine cathepsins. This work represents a key step toward the design of rapid release prodrugs or substrate-based molecular imaging probes specific to CTB.

Synthesis and evaluation of radioiodinated acyloxymethyl ketones as activity-based probes for cathepsin B

Dipeptidyl (acyloxy)methyl ketones (AOMKs) were functionalized with different iodine-containing prosthetic groups to generate a library of candidate cathepsin B probes. Compound 23a, (S)-20-[(S)-2-{[(benzyloxy)carbonyl]amino}-3-phenylpropanamido]-1-(4-iod

Modulation of the inhibitor properties of dipeptidyl (acyloxy)methyl ketones toward the CaaX proteases

Dipeptidyl (acyloxy)methyl ketones (AOMKs) have been identified as mechanism-based inhibitors of certain cysteine proteases. These compounds are also inhibitors of the integral membrane proteins Rce1p and Ste24p, which are proteases that independently mediate a cleavage step associated with the maturation of certain isoprenylated proteins. The enzymatic mechanism of Rce1p is ill-defined, whereas Ste24p is a zinc metalloprotease. Rce1p is required for the proper processing of the oncoprotein Ras and is viewed as a potential target for cancer therapy. In this study, we synthesized a small library of dipeptidyl AOMKs to investigate the structural elements that contribute to the inhibitor properties of this class of molecules toward Rce1p and Ste24p. The compounds were evaluated using a fluorescence-based in vitro proteolysis assay. The most potent dipeptidyl AOMKs contained an arginine residue and the identity of the benzoate group strongly influenced potency. A 'warhead' free AOMK inhibited Rce1p and Ste24p. The data suggest that the dipeptidyl AOMKs are not mechanism-based inhibitors of Rce1p and Ste24p and corroborate the hypothesis that Rce1p is not a cysteine protease.

Real-time monitoring of drug release

A new prodrug system, assembled using a distinctive coumarin linker, was demonstrated to report real-time activation and drug release in vitro.

Conventional Synthesis of a Selective Peptide Substrate for Measurements of Protein Kinase C

Protein kinase C (PKC), a family of serin/threonin kinases, plays a key role in signal transduction.We have prepared the PKC-selective peptide substrate H-Phe-Lys-Lys-Ser-Phe-Lys-Leu-NH2 (7) by classical solution synthesis. 7 allows PKC-measurements in cr