Novel approach nets new peptide hormones - C&EN Global

Jun 23, 1980 - Eng. News Archives ... hormones by looking for causes of observed physiological activity through isolation of compounds from active ext...
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centration, a 10 18 -gram comet would contain enough cyanide to give the oceans a concentration of 0.1 ppm to 3 ppm, depending on the degree of mixing taking place. The carbon monoxide and carbon dioxide from the comet temporarily would disturb the carbonate equilibrium in the oceans, Hsu suggests, and would alter the isotopic composition of the calcareous sediments in the oceans. This isotope change also has been observed in some ocean sediments, he says. By Hsu's model, the plants and animals of the Cretaceous period could have been killed in three ways: large land animals by atmospheric heating, marine organisms by cyanide poisoning, and calcareous marine plankton by increased dissolved carbon dioxide disturbing the carbonate equilibrium in the seawater. Strong evidence for any of the theories that involve collision of the Earth with a heavenly body would be to locate the crater the collision caused, if it still exists, Hsu says. Even more fundamental, says Alverez, is to locate more sites where the sedimentation record is intact across the

Cretaceous-Tertiary boundary and discover whether the platinum group elements are always anomalously high at this boundary. Deepsea drilling projects are already looking for more sites where this boundary is intact, he says, so further data may soon be available. Already the variation in iridium concentrations at various sites has raised some questions in the minds of some critics of an extraterrestrial explanation for the Cretaceous extinctions. A 10-km asteroid accounts nicely for the 20- to 30-fold increase in iridium found in New Zealand and Italian samples, but some sort of concentrating mechanism seems to be needed, or a larger asteroid, to explain the iridium concentrations found in Denmark and Spain. For his part, Alverez says his group is still in a position of observing the pattern of iridium at the Cretaceous-Tertiary boundary. "It's premature to say it's wrong to have more iridium in one place than another," he says. "Right now, we are just looking to see what is there. We have no preconceived level t h a t should be present." •

Novel approach nets new peptide hormones Two biochemists have reversed the usual procedure of discovering new hormones by looking for causes of observed physiological activity through isolation of compounds from active extracts. Their reverse method isolates the compounds first and looks for possible functions afterward. Kazuhiko Tatemoto and Victor Mutt of the Karolinska Institutet, Stockholm, Sweden, have isolated two peptide hormone candidates from pig intestine and brain tissue [Nature, 285, 417 (1980)]. One peptide, which they call PHI, seems related to such hormones as glucagon and secretin. The other, PYY, has an amino acid sequence that resembles that of pancreatic polypeptide. The particular variation of their method that resulted in isolation of the new peptides depends on the fact that many biologically active peptides are amides at their C-terminal ends. Tatemoto and Mutt treated tissue extracts with an enzyme that cleaves terminal amide groups, converted the resulting compounds to fluorescent 5 -dimethylamino -1 -naphthalenesulfonyl derivatives, and separated the mixture by thin-layer chromatography. In their naming system for these and other peptides yet to be discovered, P stands for peptide, the second letter stands for the N-terminal amino acid, and the third letter rep-

resents the C-terminal amino acid. Thus, P H I is the peptide with Nterminal histidine and C-terminal isoleucine amide. PYY has tyrosine at both ends. Y is tyrosine in the oneletter naming system. P H I has 27 amino acids residues. So far, the Karolinska workers have determined the sequence of the first seven and the last two. They point to similarities to corresponding sequences in glucagon, secretin, vasoactive intestinal peptide (VIP), and gastric inhibitory peptide. PHI activates adenylase cyclase in rat membranes, inhibits binding of VIP to its receptors, and stimulates insulin and glucagon release from rat pancreas. PYY has 36 amino acids. Sequences of the first nine and last two resemble those of pancreatic peptide and neurotensin. This second peptide blocks stimulation of bicarbonate secretion by secretin in cat pancreas. PYY also stimulates contracting of guinea pig gallbladder. Preliminary studies on pig brain tissue indicate that PHI and PYY are there, too. In fact, Tatemoto and Mutt say, PYY may be one of the major peptide amides of the pig brain. They measured concentrations of the peptides in tissue by determining the amounts of isoleucine or tyrosine amides cleaved from the ends of PHI and PYY by degradation with thermolysin. •

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June 23, 1980 C&EN

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