Structure‐activity and conformational studies of a series of modified C‐terminal hexapeptide neurotensin analogues

DEBORAH L. HEYL, NDREA M. SEFLER, JOHN X. HE, TOMI K. SAWYER, DAVID J. WUSTROW, HYACINTH C. AKUNNE, M. DUFF DAVIS, THOMAS A. PUGSLEY, THOMAS G. HEFFNER, ANN E. CORBIN, WAYNE L. CODY

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Neurotensin (NT), is a linear tetradecapeptide (pGlu1‐Leu2‐Tyr3‐Glu4‐Asn5‐Lys6‐Pro7‐Arg8‐Arg9‐Pro10‐Tyr11‐Ile12‐Leu13) that has been found in the central nervous system and peripheral tissues and appears to have a variety of physiological properties. A C‐terminal hexapeptide analogue [Nx‐Arg‐Lys‐Pro‐Trp‐Tle‐Leu, (1) Tle =tert‐leucine] has recently been reported to have high affinity for the NT receptor and appears to possess central activity after systemic administration. In an effort to probe the structure‐activity and conformational properties of the dipeptide, Pro‐Trp for binding and functional activity, these residues have been substituted with several natural and unnatural amino acids. Some of these analogues have binding affinities similar to compound 1, while in other cases, such as D‐amino acid substitutions, the peptides had negligible binding affinity. In general, the Pro10 position seems more tolerant of substitution by amino acids that favor a reverse turn, rather than those that favor an extended conformation. The Trp11 position accepted extra steric bulk more readily than conformational constraints.

Original languageEnglish (US)
Pages (from-to)233-238
Number of pages6
JournalInternational Journal of Peptide and Protein Research
Volume44
Issue number3
DOIs
StatePublished - Sep 1994

ASJC Scopus subject areas

  • Biochemistry

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