Hydrazone- and hydrazide-containing N-substituted glycines as peptoid surrogates for expedited library synthesis: application to the preparation of Tsg101-directed HIV-1 budding antagonists.
Replacing the Pro6 in the p6(Gag)-derived 9-mer "P-E-P-T-A-P-P-E-E" with N-substituted glycine (NSG) residues is problematic. However, incorporation of hydrazone amides ("peptoid hydrazones") can be readily achieved in library fashion. Furthermore, reduction of these hydrazones to N-substituted "peptoid hydrazides" affords a facile route to library diversification. This approach is demonstrated by application to Tsg101-binding compounds designed as potential HIV budding antagonists. [reaction: see text]
Liu
Fa
F
Laboratory of Medicinal Chemistry, CCR, National Cancer Institute-Frederick/NIH, Bldg. 376 Boyles St., Frederick, MD 21702,USA.
Stephen
Andrew G
AG
Adamson
Catherine S
CS
Gousset
Karine
K
Aman
M Javad
MJ
Freed
Eric O
EO
Fisher
Robert J
RJ
Burke
Terrence R
TR
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry*; D015497:HIV-1 / Q000187:drug effects*; D006834:Hydrazines / Q000737:chemistry; D006835:Hydrazones / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry; D019151:Peptide Library; D034444:Peptoids / Q000737:chemistry*; D011392:Proline / Q000737:chemistry; D014157:Transcription Factors / Q000378:metabolism*; D000099177:Tsg101 Protein
D019380:Anti-HIV Agents; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D005998:Glycine; D006834:Hydrazines; D006835:Hydrazones; D009842:Oligopeptides; D019151:Peptide Library; D034444:Peptoids; D011392:Proline; D014157:Transcription Factors; D000099177:Tsg101 Protein