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Biomedical subjects

D A Langs

Publications and source records attributed to D A Langs.

62 records · Page 4Linked to original sources
PubMed1977

Conformations of prostaglandin F 2alpha and recognition of prostaglandins by their receptors.

The conformation of prostaglandin F 2alpha (PGF 2alpha) has been determined by x-ray diffraction techniques. Two independent conformers of PGF 2alpha, studied as the tris(hydroxymethyl)methylamine salt, are observed to adopt the familiar "hairpin" conformation with the alpha and omega chains aligned roughly parallel. The conformers differ in ring conformation and at the C(17)-C(18) bond, one adopting a C(9) envelope ring conformation and a trans geometry at the C(17)-C(18) bond, while the other adopts a C(8) envelope ring conformation and a novel gauche geometry about C(17)-C(18). Comparison of the conformation of PGF 2alpha with that of prostaglandin E2 suggests a recognition mechanism which would permit PGF 2alpha and prostaglandin E receptors to distinguish between the two potent prostaglandins. The recognition model explains much of the binding data for the PGF 2alpha receptor in the corpus luteum and predicts the existence of an interesting PGF 2alpha analog.

Molecular Conformation↗
PubMed1977

Molecular structure of thyroxine analogues. Crystal structure of 3,5,3'-triiodothyroacetic and 3,5,3',5'-tetraoiodothyroacetic acid N-diethanolamine (1:1) complexes.

Crystallographic data demonstrated that conformations of thyroid hormones and their derivatives in which the phenyl rings are either skewed (phi,phi'; +/-90,0 degrees) or twist-skewed (phi,phi'; +/-108, +/-28 degrees) are energetically favored. Acetic acid metabolites are consistently observed in the skewed conformation whereas their parent hormones are observed in the twist-skewed conformation. These preferences are manifestations of long-range conformational transmission and together with plasma protein binding data may indicate a site-specific preference for the skewed vs. twist-skewed conformation. These findings result in part from the crystal structure determinations of the N-diethanolamine (1:1) complexes of the active thyroxine metabolites 3,5,3'-triiodothyroacetic acid (T3AA) and 3,5,3'5'-tetraiodothyroacetic acid (T4AA) which are reported here. The conformation of the 3'-iodine in the hypocholestermic agent T3AA is distal, the biologically preferred conformation, and the overall conformation of T3AA is transoid, while that of T4AA is cisoid.

Chemical Phenomena↗
PubMedDate not supplied

Pharmacologic and radioligand binding analysis of the actions of 1,4-dihydropyridine activators related to Bay K 8644 in smooth muscle, cardiac muscle and neuronal preparations.

The structure-activity relationships of a series of 1,4-dihydropyridine Ca2+ channel activators, including Bay K 8644, have been determined by pharmacologic and radioligand binding techniques. Pharmacologic techniques included tension responses and the measurement of pA2 values for nifedipine antagonism of Bay K 8644 responses in guinea pig ileal, rat femoral and rat atrial and papillary muscle preparations. Radioligand binding experiments employed competition against [3H]nitrendipine binding in ileal smooth muscle and rat ventricular membranes and rat brain synaptosomal preparations. The series of compounds was employed as the racemates. Binding affinities were not significantly different between smooth muscle, cardiac muscle and brain preparations and the same rank order of pharmacologic activities is observed in smooth and cardiac muscle, where the effects of the 4-phenyl substituents, o greater than or equal to m greater than p, parallel those observed for 1,4-dihydropyridine antagonists. In the ileal and femoral artery smooth muscle preparations a 1:1 correlation is observed between pharmacologic and radioligand binding affinities. However, in the cardiac muscle preparations, left atrium and papillary muscle, there is an approximately 10-fold difference between the binding affinities and the lower pharmacologic affinities. A similar difference between smooth and cardiac muscle is observed with the pA2 values of 6.97 and 7.06 in atrial and papillary muscle respectively, which are significantly lower than the values of 8.54 and 8.72 measured in ileal and femoral artery respectively. The structure-activity expressions measured for this small series of 1,4-dihydropyridine activators parallel those observed in the larger series of 1,4-dihydropyridine antagonists. This is consistent with proposals that activators and antagonists interact at common binding sites that are components of a voltage-dependent Ca2+ channel.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMedDate not supplied

Molecular structure and mechanisms of action of cyclic and linear ion transport antibiotics.

As a direct result of the vision, determination, and magnetic personality of Yuri Ovchinnikov a collaboration between the Shemyakin Institute of Bioorganic Chemistry and the Medical Foundation of Buffalo was begun in the early 1970's. The collaboration generated valuable insight into the structural basis for the capture, transport, and release of ions by ion transport antibiotics and the basis for the ion selectivity of these compounds. The collaboration produced dozens of joint publications on the structure and function of cyclic and linear ion transport antibiotics, fostered fruitful exchange visits between scientists in the two Research Institutes and has been a major source of creativity in my scientific career and those of many of my colleagues in Buffalo. This review summarizes major accomplishments of the collaboration.

Amino Acid Sequence↗