Abstract：
:T22 ([Tyr5,12,Lys7]-polyphemusin II) has been shown to have strong anti-human immunodeficiency virus (HIV) activity comparable to that of 3'-azido-2',3'-dideoxythymidine (AZT). T22, an 18-residue peptide amide, takes an antiparallel beta-sheet structure that is maintained by two disulfide bridges. Herein we synthesized several shortened analogs of T22 in order to search for a more suitable lead compound. A 14-residue analog having one disulfide bridge, TW70 (des-[Cys8,13, Tyr9,12]-[D-Lys10, Pro11]-T22), was found to have highly potent activity comparable to that of T22, and to take an antiparallel beta-sheet structure similar to that of T22. This indicates that the molecular size of T22 can be reduced without loss of activity or significant change in the secondary structure, and that TW70 may represent a novel lead compound. Furthermore, modifying the N-terminal alpha-amino group of TW70 with a fluoresceinthiocarbamoyl group, and the epsilon-amino group of D-Lys8 at the turn portion with a 5-aminopentanoyl group remarkably increased the selectivity index (50% cytotoxic concentration/50% effective concentration).
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Tamamura H,Waki M,Imai M,Otaka A,Ibuka T,Waki K,Miyamoto K,Matsumoto A,Murakami T,Nakashima H,Yamamoto N,Fujii Ndoi
10.1016/s0968-0896(97)10055-4subject
Has Abstractpub_date
1998-04-01 00:00:00pages
473-9issue
4eissn
0968-0896issn
1464-3391pii
S0968089697100554journal_volume
6pub_type
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