171858-39-2

Upstream product

• 3978-80-1 Boc-Tyr-OH 
• 171858-38-1 3-<amino>-1-bromopropane 
• 13139-16-7 N-(tert-butyloxycarbonyl)-L-isoleucine 

Downstream Products

• 171858-47-2 (S)-2-Acetylamino-4-methyl-pentanoic acid ((S)-1-{(S)-1-benzyl-3-[(8S,11S)-8-((S)-sec-butyl)-7,10-dioxo-2-oxa-6,9-diaza-bicyclo[11.2.2]heptadeca-1⁽¹⁶⁾,13⁽¹⁷⁾,14-trien-11-ylamino]-2-oxo-propylcarbamoyl}-2-methyl-propyl)-amide 
• 171858-52-9 (2R,3S,11'S,8'S)-3-(tert-butoxycarbonylamino)-4-phenyl-1-<<7',10'-dioxo-8'-(1-methylpropyl)-2'-oxa-6',9'-diazabicyclo<11.2.2>heptadeca-13',15',16'-trien-11'-yl>amino>butan-2-ol 

Relevant academic research and scientific papers

Substrate-based cyclic peptidomimetics of Phe-Ile-Val that inhibit HIV-1 protease using a novel enzyme-binding mode

Results are presented for inhibitors of HIV-1 protease that demonstrate a new strategy for developing peptidomimetics, involving the replacement of flexible segments of peptide substrates with conformationally constrained hydrolytically-stable macrocyclic

Regioselective structural and functional mimicry of peptides. Design of hydrolytically-stable cyclic peptidomimetic inhibitors of HIV-1 protease

Hydrolytically-stable cyclic mimetics of the tripeptides Leu-Asn-Phe and Phe-Ile-Val were designed and incorporated into peptidic inhibitors, Ac-{Leu-Asn-Phe}-CHOHCH2-Pro-Ile-Val-NH2 and Ac-Leu-Val-Phe-CHOHCH2-{Phe-Ile-Val}-NH2, of HIV-1 protease. Structural mimicry has been established through molecular modeling and X-ray crystallographic studies of inhibitors bound to HIV-1 protease. Cyclic and acyclic inhibitors had similar conformations that were superimposable and formed similar interactions with the enzyme. Functional mimicry was demonstrated by comparable inhibition of the protease by acyclic and cyclic molecules. Further substitution of the residual acyclic Pro-Ile-Val or Leu-Val-Phe inhibitor components, with Pip-NHtBu or Boc-Phe, respectively, gave hydrolytically stable, water-soluble, lipophilic inhibitors of similar potency. The use of cycles to fix the conformations of amino acid sequences in peptides allows regioselective structural mimicry leading to functional mimicry and also permits localized structure-activity optimization in inhibitors of HIV-1 protease. This approach might be usefully applied to inhibitors of other proteins.