A novel inhibitor of angiotensin I converting enzyme (ACE), designated K-26, was isolated from the broth filtrate of an actiomycete K-26. K-26 is a water soluble, acidic peptide composed of an equal mol of L-isoleucine, L-tyrosine and l(R)-l-amino-2-(4-hydroxyphenyl)-ethylphosphonic acid. The IC50 of K-26 for ACE inhibition was 6.7 ng/ml when hippuryl-Lhistidyl-L-leucine was used as a substrate of ACE. K-26 possesses hypotensive activity in vivo.Angiotensin I converting enzyme (ACE) has been found to play a critical role in the regulation of blood pressure in man and animals.Ever since the discovery of captoprill1) a specific inhibitor of ACE, and its successful application to the therapy of hypertension, attempts have been made to develop
1 The gastrointestinal motor stimulating action of the motilin analogue, , was investigated both in the anaesthetized rabbit and in rabbit isolated smooth muscle tissues. 2 i.v.) produced motor stimulating actions in the gastric antrum, ileum and descending colon, the excitatory responses of which were initiated at the same time but declined with different time courses. The rank order of the excitatory response was: descending colon > gastric antrum >> ileum. 3 Atropine (1-3 mg kg-', i.v.) or naloxone (1 mg kg-', i.v.) completely suppressed the excitatory response to KW-5139 in the gastric antrum, but only partially attenuated that in the descending colon. This suggests that the mechanism of the excitatory response is different in the gastric antrum and the descending colon, and that cholinergic neural pathway is involved in the response of the gastric antrum.4 KW-5139 (0.1 nM-I J1M) caused concentration-dependent contractions of the gastric antrum, duodenum, jejunum, ileum and the descending colon in vitro. In the rabbit intestine, the contractile response to KW-5139 was strongest in the duodenum and weakest in the ileum.
5The contractile response to KW-5139 in the intestinal segments were not affected by tetrodotoxin, but were decreased by verapamil, or pretreatment with a high concentration of porcine motilin, confirming the involvement of motilin receptors in the response to The present results suggest that the rabbit is a suitable species for the investigation of motilin on gut motility, because of the high responsiveness of the descending colon as well as the upper gastrointestinal tract.
Infrared absorption spectra have been observed in the 4000–500 cm−1 region of deuterated and undeuterated films of deoxyribonucleic acids (DNA’s) obtained from Micrococcus lysodeikticus (guanine plus cytosine content or GC content 72%), from Bacille de Calmette-Guérin (GC 65%), from Pseudomonas aeruginosa (GC 65%, 15N-substituted), from calf thymus (GC 44%), and from Cancer borealis (GC 3%). Of the undeuterated DNA, 14 absorption bands have been assigned to the GC pair and 17 absorption bands to the adenine-thymine (AT) pair. Of the deuterated DNA, 19 absorption bands have been assigned to the GC pair and 16 to the AT pair. For 4 bands of undeuterated DNA and 13 bands of deuterated DNA, appreciable 15N isotopic shifts have been observed. A discussion has been given of a few of these bands on the basis of the observed 15N shift and some other data.
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