69531-03-9

Upstream product

• 3160-59-6 N-Cbz-L-Isoleucine 
• 2748-02-9 L-leucine tert-butyl ester hydrochloride 
• 146286-84-2 Z-Ile-NCA 

Downstream Products

• 182371-42-2 (S)-2-[(2S,3S)-2-(2-Hydroxycarbamoylmethyl-3-phenyl-propionylamino)-3-methyl-pentanoylamino]-4-methyl-pentanoic acid tert-butyl ester 

Relevant academic research and scientific papers

Rapid, one-pot synthesis of urethane-protected tripeptides

Urethane-protected tripeptides are synthesized in solution, without isolation of purification of intermediates, using urethane-protected N-carboxyanhydrides as coupling reagents and hydrogenation for removal of N-protection.

Module assembly for protein-surface recognition: Geranylgeranyltransferase I bivalent inhibitors for simultaneous targeting of interior and exterior protein surfaces

Synthetic chemical probes designed to simultaneously targeting multiple sites of protein surfaces are of interest owing to their potential application as site specific modulators of protein-protein interactions. A new approach toward bivalent inhibitors of mammalian type I geranylgeranyltransferase (GGTase I) based on module assembly for simultaneous recognition of both interior and exterior protein surfaces is reported. The inhibitors synthesized in this study consist of two modules linked by an alkyl spacer; one is the tetrapeptide CVIL module for binding to the interior protein surface (active pocket) and the other is a 3,4,5-alkoxy substituted benzoyl motif that contains three aminoalkyl groups designed to bind to the negatively charged protein exterior surface near the active site. The compounds were screened by two distinct enzyme inhibition assays based on fluorescence spectroscopy and incorporation of a [ 3H]-labeled prenyl group onto a protein substrate. The bivalent inhibitors block GGTase I enzymatic activity with Ki values in the submicromolar range and are approximately one order of magnitude and more than 150 times more effective than the tetrapeptide CVIL and the methyl benzoate derivatives, respectively. The bivalent compounds 6 and 8 were shown to be competitive inhibitors, suggesting that the CVIL module anchors the whole molecule to the GGTase I active site and delivers the other module to the targeting protein surface. Thus, our module-assembly approach resulted in simultaneous multiple-site recognition, and as a consequence, synergetic inhibition of GGTase I activity, thereby providing a new approach in designing protein-surface-directed inhibitors for targeting protein-protein interactions.

Synthesis and Analgesic Effects of N--1-oxo-2(R)-benzylpropyl>-L-isoleucyl-L-leucine, a New Potent Inhibitor of Multiple Neurotensin/Neuromedin N Degrading Enzymes

The synthesis of N--1-oxo-2(R)-benzylpropyl>-L-isoleucyl-L-leucine (JMV-390-1, 6a), a multipeptidase inhibitor based on the C-terminal sequence common to neurotensin (NT) and neuromedin N (NN), is described.This compound behaves as a full inhibitor of the major NT/NN degrading enzymes in vitro, e.g. endopeptidase 24.16, endopeptidase 24.15, endopeptidase 24.11, and leucine aminopeptidase (type IV-S), in the nanomolar range (IC50's from 30 to 60 nM).Compound 6a was found to increase endogenous recovery of NT and NN from slices of micehypothalamus depolarized with potassium.In various assays commonly used to select analgesics, e.g. hot-plate test, tail-flick test, acetic acid-induced writhing test, in mice, compound 6a proved to be potent when intracerebroventricularly (icv) injected.The analgesic effects observed were totally (hot-plate test) or largely (tail-flick test) reversed by the opioid antagonist naltrexone.Furthermore, icv injection of compound 6a (10 μg/mouse) was found to significantly potentiate the hypothermic effects of NT or NN.