Neurotensin degradation by soluble and membrane-associated enzymes from the brain

Emson, Piers C.; Checler, Frédéric; Camargo, Aline Cristina; Pittaway, K.; Williams, Betty J.; Kitabgi, Patrick; Vincent, Jean‐Pierre

doi:10.1042/bst0130053

Cited by 7 publications

(1 citation statement)

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“…As a result, it can be concluded that concomitant substitution at the Arg- (8) and Ile (12) positions with non-natural amino acids completely prevents peptidase degradation in rat serum. Prior studies have demonstrated the Arg(8)-Arg( 9) and the Tyr(11)-Ile (12) bond to be major sites of peptide cleavage in the brain; [45][46][47][48][49][50] hence, it is hypothesized that these peptides will be resistant to peptidases in the brain. Modifications of this method in order to quantify NT [8][9][10][11][12][13] and KK1-19 in brain homogenate are currently under investigation.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Analysis of Stable, Receptor-Selective Neurotensin[8−13] Analogues

et al. 2003

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A set of neurotensin[8-13] (NT[8-13]) analogues featuring substitution of non-natural cationic amino acids in the Arg(8) position have been synthesized and tested for binding potencies against the three cloned human NT receptors (hNTR-1, hNTR-2, hNTR-3), functional agonism of the hNTR1 and for rat serum stability. Three distinct classes of peptides have been identified: Class 1 features alkyl-Arg analogues at Arg(8), Class 2 features alpha-azido-cationic amino acids at Arg(8), and Class 3 feature modified Arg(8) and Tyr(11) residues. Most of the peptides maintain or exceed the binding potency of NT[8-13] to hNTR-1. Class 2 analogues exceed the binding potency of NT[8-13] to hNTR-2 with KK19 binding with higher affinity to hNTR-2 than hNTR-1. Peptides with enhanced binding potencies for hNTR-3 were not found. All analogues are functional agonists of the hNTR1 receptor as indicated by phosphoinositide (PI) determination. Serum stability increased with peptide classification where the half-life of Class 1 < Class 2 < Class 3 which are stable to rat serum for > 24 h.

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