Abstract
HIV-1 viral budding involves binding of the viral Gag(p6) protein to the ubiquitin E2 variant domain of the human tumor susceptibility gene 101 protein (Tsg101). Recognition of p6 by Tsg101 is mediated in part by a proline-rich motif that contains the sequence 'Pro-Thr-Ala-Pro' ('PTAP'). Using the p6-derived 9-mer sequence 'PEPTAPPEE', we had previously improved peptide binding affinity by employing N-alkylglycine ('peptoid') residues. The current study applies ring-closing metathesis macrocyclization strategies to Tsg101-binding peptide-peptoid hybrids as an approach to stabilize binding conformations and to observe the effects of such macrocyclization on Tsg101-binding affinity and bioavailability.
Published by Elsevier Ltd.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
MeSH terms
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Amino Acid Sequence
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DNA-Binding Proteins / antagonists & inhibitors*
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DNA-Binding Proteins / metabolism
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Endosomal Sorting Complexes Required for Transport / antagonists & inhibitors*
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Endosomal Sorting Complexes Required for Transport / metabolism
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Fluorescent Dyes / chemistry
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HeLa Cells
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Humans
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Macrocyclic Compounds / chemical synthesis
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Macrocyclic Compounds / chemistry*
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Macrocyclic Compounds / pharmacology
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Peptides / chemical synthesis
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Peptides / chemistry*
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Peptides / pharmacology
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Peptoids / chemical synthesis
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Peptoids / chemistry*
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Peptoids / pharmacology
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Protein Binding
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Transcription Factors / antagonists & inhibitors*
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Transcription Factors / metabolism
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gag Gene Products, Human Immunodeficiency Virus / metabolism
Substances
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DNA-Binding Proteins
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Endosomal Sorting Complexes Required for Transport
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Fluorescent Dyes
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Macrocyclic Compounds
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Peptides
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Peptoids
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Transcription Factors
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Tsg101 protein
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gag Gene Products, Human Immunodeficiency Virus