Introduction of the new dipeptide isostere 7-endo-BtA as reverse turn inducer in a Bowman-Birk proteinase inhibitor: synthesis and conformational analysis.
Two dipeptide isosteres 7-exo-BTG (1) and 7-endo-BtA (2), belonging to the new class of gamma/delta-bicyclic amino acid BTAa, were inserted into an 11-residue peptide deriving from the Bowman Birk Inhibitor (BBI) class of serine protease inhibitors, and the conformational properties of these modified peptides have been studied by NMR and molecular modelling. The dipeptide isostere 7-endo-BtA [(1R,4S,5R,7R)-4-endo-methyl-6,8-dioxa-3-azabicyclo[3.2.1]octane-7-endo-carboxylic acid] (2), derived from L-alanine and meso tartaric acid, gave rise to the modified BBI peptide 5 whose structure was very similar to that of the original peptide 3, suggesting a possible reverse turn inducing property for this dipeptide isostere.
Scarpi
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Department of Chemistry, Imperial College of Science Technology and Medicine, South Kensington, London SW7 2AY, UK.
Occhiato
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EG
Trabocchi
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A
Leatherbarrow
R J
RJ
Brauer
A B
AB
Nievo
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M
Guarna
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A
D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000737:chemistry*
C435827:H-Ser-Cys-Thr-Phe-Ser-7-endo-BtA-Pro-Gln-Cys-Tyr-OH; D009842:Oligopeptides; D011480:Protease Inhibitors; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D002918:Chymotrypsin; C117608:alpha-chymotrypsin