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Glycine-amide is an active metabolite of the antiretroviral tripeptide glycyl-prolyl-glycine-amide.

Artikel i vetenskaplig tidskrift
Författare Elin Andersson
Peter Horal
Alenka Jejcic
Stefan Höglund
Jan Balzarini
Anders Vahlne
Bo Svennerholm
Publicerad i Antimicrobial agents and chemotherapy
Volym 49
Nummer/häfte 1
Sidor 40-4
ISSN 0066-4804
Publiceringsår 2005
Publicerad vid Institutionen för laboratoriemedicin, Avdelningen för klinisk virologi
Sidor 40-4
Språk en
Länkar dx.doi.org/10.1128/AAC.49.1.40-44.2...
Ämnesord Animals, Anti-HIV Agents, pharmacology, Cell Line, Cells, Cultured, Drug Resistance, Viral, Glycine, analogs & derivatives, pharmacology, HIV-1, drug effects, physiology, Humans, Leukocytes, Mononuclear, virology, Microbial Sensitivity Tests, Oligopeptides, metabolism, pharmacology, Serial Passage, Virus Assembly, drug effects, Virus Replication, drug effects
Ämneskategorier Medicin och Hälsovetenskap

Sammanfattning

The chemically modified tripeptide glycyl-prolyl-glycine-amide (GPG-NH(2)) inhibits replication of human immunodeficiency virus (HIV) type 1 (HIV-1) in vitro, probably by interfering with capsid formation. The aim of the present study was to determine whether the metabolites glycyl-proline (GP-OH), glycine (G-OH), prolyl-glycine-amide (PG-NH(2)), proline (P-OH), and glycine-amide (G-NH(2)) from proteolytic cleavage may inhibit the replication of HIV-1 in vitro. PG-NH(2) has previously been shown to have a modest effect on HIV-1 replication. In the present study we show that G-NH(2) exhibits a pronounced inhibitory effect on HIV-1. This effect was not due to a decrease in cell proliferation or viability and could not be shown for herpes simplex virus type 1. The G-NH(2) concentration that inhibited virus replication by 50% (IC(50)) was equimolar to that of GPG-NH(2) and ranged from 3 to 41 microM. Transmission electron microscopy revealed that the effect of G-NH(2) on HIV-1 morphology was equivalent to that of GPG-NH(2) and showed disarranged capsid structures, indicating interference with capsid formation. Serial passage of HIV-infected cells with G-NH(2) for more than 20 subcultivations did not decrease the susceptibility to the compound. The results from this study suggest that GPG-NH(2) might act as a prodrug and that G-NH(2) is an active antiretroviral metabolite.

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http://www.gu.se/forskning/publikation/?publicationId=54996
Utskriftsdatum: 2020-02-22