42362-08-3

Upstream product

• 1161-13-3 N-Cbz-L-Phe 
• 2389-48-2 N-ε-tert-butoxycarbonyl-L-lysine methyl ester hydrochloride 
• 3017-32-1 (S)-methyl 2-amino-6-(tert-butoxycarbonylamino)hexanoate 

Downstream Products

• 1451453-87-4 2S-(2S-benzyloxycarbonylamino-3-phenylpropanamido)-6-(tert-butoxycarbonylamino)hexanol 

Relevant academic research and scientific papers

LIVER X RECEPTOR AGONISTS AND USES THEREOF

Disclosed herein are antibody drug conjugates having an antibody or antibody fragment that binds a cell surface molecule on a target cell, wherein the target cell is a lymphocyte and a therapeutic agent that has a therapeutic effect in a subject in need t

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

Vinyl sulfone-based peptidomimetics as anti-trypanosomal agents: Design, synthesis, biological and computational evaluation

A series of vinyl sulfone-containing peptidomimetics were rationally designed, synthesized, and evaluated against Trypanosoma brucei brucei. These electrophilic compounds are likely to exert their antitrypanosomal activity via inhibition of trypanosomal cysteine proteases, TbCatB and rhodesain, through alkylation of a key cysteine residue within the protease active site. The series was designed to present complementary groups to naturally recognized peptide substrates while probing tolerance to a range of substitutions at the P1, P1′, and P2 positions. The most potent compound, 29 (EC50 = 70 nM, T. b. brucei whole cell assay), displayed minimal toxicity (>785 times selectivity) when assayed for cytotoxicity against the human promyelocytic leukemia (HL-60) cell line. Cells treated with compound 29, as with K777 (2), exhibited an increase in both the number of multinucleated cells and cells with swollen flagellar pockets. Computational analysis revealed a strong correlation between the hypothetical binding mode in TbCatB/rhodesain and trypanocidal activity in vitro.

Synthesis and optimization of hyaluronic acid-methotrexate conjugates to maximize benefit in the treatment of osteoarthritis

We previously reported that a conjugate of hyaluronic acid (HA) and methotrexate (MTX) could be a prototype for future osteoarthritis drugs having the efficacy of the two clinically validated agents but with a reduced risk of the systemic side effects of MTX by using HA as the drug delivery carrier. To identify a clinical candidate, we attempted optimization of a lead, conjugate 1. Initially, in fragmentation experiments with cathepsins, we optimized the peptide part of HA-MTX conjugates to be simpler and more susceptible to enzymatic cleavage. Then we optimized the peptide, the linker, the molecular weight, and the binding ratio of the MTX of the conjugates to inhibit proliferation of human fibroblast-like synoviocytes in vitro and knee swelling in rat antigen-induced monoarthritis in vivo. Consequently, we found conjugate 30 (DK226) to be a candidate drug for the treatment of osteoarthritis.

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