Bioorganic synthesis of a recombinant HIV-1 fusion inhibitor, SC35EK, with an N-terminal pyroglutamate capping group.
The bioorganic synthesis of an end-capped anti-HIV peptide from a recombinant protein was investigated. Cyanogen bromide-mediated cleavage of two Met-Gln sites across the target anti-HIV sequence generated an HIV-1 fusion inhibitor (SC35EK) analog bearing an N-terminal pyroglutamate (pGlu) residue and a C-terminal homoserine lactone (Hsl) residue. The end-capped peptide, pGlu-SC35EK-Hsl, had similar bioactivity and biophysical properties to the parent peptide, and an improved resistance to peptidase-mediated degradation was observed compared with the non-end-capped peptide obtained using standard recombinant technology.
Kajiwara
Kazumi
K
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Watanabe
Kentaro
K
Tokiwa
Rei
R
Kurose
Tomoko
T
Ohno
Hiroaki
H
Tsutsumi
Hiroko
H
Hata
Yoji
Y
Izumi
Kazuki
K
Kodama
Eiichi
E
Matsuoka
Masao
M
Oishi
Shinya
S
Fujii
Nobutaka
N
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002942:Circular Dichroism; D023581:HIV Fusion Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D011761:Pyrrolidonecarboxylic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011994:Recombinant Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization
D023581:HIV Fusion Inhibitors; D011994:Recombinant Proteins; C088386:homoserine lactone; D015107:4-Butyrolactone; D011761:Pyrrolidonecarboxylic Acid