P-Receptor affinity

Opioid receptor binding Diamorphine (Inturrisi et al., 1983) has a 10-100fold lower p-opioid receptor binding affinity than morphine. The relevant opioid properties originate from the high p-receptor affinity of the metabolites 6-acetylmorphine and morphine (Umans and Inturrisi, 1981). 

Opioid receptor binding Meptazinol (Holmes and Ward, 1985) is a partial p-agonist with a high p-receptor affinity the selective action at a special p1-subtype is controversial (Pasternak et al., 1985). 

Molecular Model for an Anionic Opiate p,-Receptor—Affinity and Activation of Morphine Conformers. 

The requirement for a phenol for opioid receptor interaction was recently revisited in a series of cyclazocine analogs in which the hydroxyl was replaced by a primary, secondary or tertiary amino group (399) and several of these analogs retained high affinity for opioid receptors the same modificationsto morphine decreased p-receptor affinity by at least 35-fold (400). 

The C-terminal extension of Tyr-Tic and Dmt-Tic can also enhance p-receptor affinity. The dipeptide derivative Dmt-Tic- NH (CH2)3Ph is a 6-receptor antagonist and /a-re-ceptor agonist (867). Interestingly, Dmt-Tic-NH-l-adamantane is a weak agonist at 6 re-eeptors and potent agonist at p receptors, although its affinity for the two receptors is... 

Extension of dermorphin with residues from the precursor sequence also yields potent p-selective peptides. Although introduction of the additional residues through the Glu or Ala residues decreases p-receptor affinity, apparently because of introduction of the acidic Glu residue, further extension of the sequence increases p-receptor affinity as basic residues are incorporated (872) the resulting pentadecapeptide (Tyr-o-Ala-Phe-Gly-Tyr-Pro-Ser-Gly-Glu-Ala-Lys-Lys-Ile-Lys-Arg-NH2) has exceptional affinity for /x receptors... 

CTAP (20), respectively (105,941), which exhibit greatly reduced affinity for somatostatin receptors and enhanced affinity and selectivity for /X receptors. Analysis of CTP by NMR suggested that the central Tyr-o-Trp-Lys-Thr sequence adopts a type IF /3 turn (942). The conformationof these peptides was further restricted and preceptor selectivity further enhanced by incorporation of the constrained amino acid o-Tic in position 1 the resulting peptides TCTP, TCTOP, and TCTAP are potent p antagonists with exceptional selectivity for jLL receptors (Table 7.21) (943,944). Incorporation of either isomer of -Me-n-Phe in position 1 decreases p-receptor affinity and selectivity 10- and 40-fold, respectively (945). 

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