Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three classes of flexible opiates have been studied: 4-phenyl piperdines, methadone and enkephalins. Our results show that low energy conformers of the 4-phenyl piperidines have equatorial phenyl rings and cannot completely overlap with rigid opiates at the receptor. A combination of calculated conformational and electronic properties could account for observed potency differences in meperidine, desmethyl, alpha+, alpha-, beta+ and beta- prodines. Our results also indicate that both meperidine and its reverse ester bind to the receptor in a similar mode with the phi ring in approximmately the same position as the phenyl substituent in 5-phenyl benzomorphans. Conformers of methadone which maximally resemble morphine have very high relative energies. The lowest energy conformer has a partial H-bond between the NH and O=C groups. In this conformation methadone resembles meperidine more than morphine. The electronic structure of all three types of opiates indicate a similar cationic charge distribution around the amine nitrogen and imply that their binding to an anionic receptor site could be similar. The determination of peptide opiate conformations present a challenge of a different order of magnitude than the most flexibe exogenous opiates. Because of the extremely large number of possible conformations, search strategies based on energy optimized conformations alone are not adequate to select plausible receptor site candidates. Other criteria such as consistency with known structure activity data and similarities to rigid opiates must be used. With this rationale, we have predicted and characterized a low energy conformer of Met-enkephalin and D-ala2 Met-enkephalin as a likely candidate at the receptor site. With a modest energy input (deltaE approximately 3 kcal/mole) significant overlap of this conformer with the potent opiate PET was obtained. The tyrosine and phenyalanine side chains and the terminal amine and carboxyl groups play a crucial role in this overlap. It is hoped that this calculation with help establish a template for peptide opiate receptor interactions.
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PMID:Structure-activity studies of narcotic agonists and antagonists from quantum chemical calculations. 21 25

To elucidate the role of Met-enkephalin in the hypertension in spontaneously hypertensive rats, the depressor response to Met-enkephalin was compared between normotensive (Wistar) and spontaneously hypertensive rats by administration of bestatin (1.25 mg) as a component of a mixture of enkephalinase inhibitors. All experiments were performed under anesthesia by intraperitoneal injection of pentobarbital (50mg/kg). Catheters were connected to the arterial and venous lines for blood pressure recording and administration of drugs. Hypotensive effects of injected Met-enkephalin were noticeably enhanced by administration of bestatin compared with pre-bestatin responses at each dose of Met-enkephalin(10, 25, 50, and 100n mol). We could not find any statistically significant difference between blood pressure responses to 25n mole Met-enkephalin in Wistar and spontaneously hypertensive rats both before and after administration of bestatin. Our present study dose not suggest the active role of Met-enkephalin in the hypertension of spontaneously hypertensive rats.
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PMID:A comparison of the hypotensive effects of Met-enkephalin in normotensive and spontaneously hypertensive rats. 274 99

We described here a new immunization procedure to obtain high titre and high specific antibodies against Leu-enkephalin (LE). The immunogen form is composed of one part of LE conjugate and one part of LE-Arg6 conjugate. We have observed an increase of titre, affinity and specificity of the antibodies in the coimmunization procedure compared to those obtained by conventional immunization involving only the LE conjugate. The Leu-enkephalin antibodies exhibit a high affinity (KD 8 X 10(-12) M) and we are able to detect the Leu-enkephalin at the 10(-15) mole level. These LE antibodies are highly specific of the C part of LE peptide and cross-react weakly with Met-enkephalin (1%).
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PMID:A new immunization procedure for the obtention of anti-leucine enkephalin antibodies. Part I. Immunization procedure and physicochemical characteristics of antibodies. 378 85