Dynorphin analogs

Reverses the agonist aetivity of Dyn A-(1-13)NH2 in an adenylyl cyclase assay using cloned k receptors, values against U50,488 and a dynorphin analog, respectively. 

The peptide (3 -iodo Tyr1 )-D-Pro10-dynorphin A [1-11] had a potent K value of 0.21 nM (Table 3), which was similar to the Kd of its radioactive analog (0.16 nM). Of the kappa-selective ligands, U-50,488 and U-69,593 were... 

The so far neglected K-receptors also appear to relate to specific peptides, namely, dynorphin g and its 1-9 analog, which are selective ligands for such sites, more fully discussed elsewhere (p. 361, 439).(110)... 

Dynorphin A with a diiodotyrosine at posihon 1 was synthesized by using A -Boc solid-phase chemistry (130), and many other syntheses of the peptide and its analogs also were reported. An optimized A -Fmoc chemistry synthesis... 

Turcotte A, Lalonde JM, St. Pierre S, LeMaire S. Dynorphin-(1-13). I. Structure-function relationships of Ala-containing analogs. Int. J. Peptide Protein Res. 1984 23 361-367. 

Linear Analogs. Early structural modifications were made in the C-terminal "address" sequence of dynorphin A (263) and focused on the nonbasic residues (see Refs. 656, 753). D-Pro was incorporated in place of Pro ° in both dynorphin A-(1-11) (768)and A-( 1 -13) (769) and was reported to enhance K-receptor selectivity (see Table 7.17). Ala and o-Ala were substituted for He with retention of K-recep-tor affinity and selectivity (769,770). Replacement of the basic residues individually by iV -acetylated lysine (771) indicated that... 

Table 7.17 Opioid Receptor Affinities and Opioid Activity in the GPI and MVD of Analogs of Dynorphin A (Dyn A)...

Conformationally Constrained Analogs. Local constraints have been incorporated into dynorphin A. The conformational ly constrained phenylalanine derivative Ate (2-aminotetralin-2-carboxylicacid. Fig. 7.43) has been incorporated in [D-Ala ]dynorphin A-(l-... 

Dynorphin A Analogs with Antagonist Activity. Early attempts to prepare K-selective... 

A Boc-protected tetrapeptide derived from a sequence found in Philippine cobra venom has been reported to have weak antagonist activity at K receptors (807). Attachment of the C-terminal "address" sequence of [o-Ala ]-dynorphin A-d-lDNHg to this sequence resulted in a novel acetylated dynorphin A analog, JVA-901 (now referred to as venorphin). 

B. Vig, Synthesis and Pharmacological Evaluation of Dynorphin A Analogs Constrained in the "Message" Sequence, Ph.D. thesis. University of Maryland Baltimore, 2001. 

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