Solution-phase synthesis of an anti-human immunodeficiency virus peptide, T22 ([Tyr5,12,Lys7]-polyphemusin II), and the modification of Trp by the p-methoxybenzyl group of Cys during trimethylsilyl trifluoromethanesulfonate deprotection.
T22 ([Tyr5,12,Lys7]-polyphemusin II) was previously synthesized by a solid-phase method and was found to have a strong anti-human immunodeficiency virus (HIV) activity, comparable to that of 3'-azido-2',3'-dideoxy-thymidine (AZT). In the present study, the solution-phase synthesis of T22 was attempted in order to produce this peptide on a large scale. An 18-residue peptide amide corresponding to the entire amino acid sequence of T22 was synthesized by assembling four peptide fragments and two amino acid derivatives, followed by thioanisole-mediated deprotection with 1 M trimethylsilyl trifluoromethanesulfonate (TMSOTf) in trifluoroacetic acid followed by air-oxidation. During this deprotection, a significant by-product derived from the transfer of the p-methoxybenzyl (MBzI) group from the sulfhydryl group of the cysteine residue to the side chain of the tryptophan residue was formed. This side reaction was found to be efficiently suppressed by adopting a two-step deprotection procedure using silver trifluoromethanesulfonate (AgOTf)-TMSOTf or trimethylsilyl bromide (TMSBr)-TMSOTf.
Tamamura
H
H
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Otaka
A
A
Takada
W
W
Terakawa
Y
Y
Yoshizawa
H
H
Masuda
M
M
Ibuka
T
T
Murakami
T
T
Nakashima
H
H
Waki
M
M
D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents / Q000138:chemical synthesis*; D003545:Cysteine / Q000737:chemistry*; D006678:HIV / Q000187:drug effects*; D008698:Mesylates / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis*; D014297:Trimethylsilyl Compounds / Q000737:chemistry*; D014364:Tryptophan / Q000737:chemistry*
D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents; D008698:Mesylates; D010455:Peptides; D014297:Trimethylsilyl Compounds; C076963:T22 protein, synthetic; C053353:trimethylsilyl trifluoromethanesulfonate; D014364:Tryptophan; D003545:Cysteine