PHARMACOLOGY: Code Word of Memory - C&EN Global Enterprise

Feb 9, 1970 - Another chapter has been added to the story of memory with the announcement from Dr. Georges Ungar of Baylor University medical school, ...
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PHARMACOLOGY:

Code Word of Memory Another chapter has been added to the story of memory with the announcement from Dr. Georges Ungar of Baylor University medical school, Houston, Tex,, that he has determined the composition and sequence of amino acids of what may well be the first of many chemical code words that control memory and learning. The announcement came last week at the Western Pharmacology Society meeting in San Diego, Calif. Members of the Baylor research team include Dr. Ing-Kang, Dr. Dominic Desiderio, and Louis Galvan. The material, which comprises 14 amino acids, is probably the first member of a very important family of substances which serve for the coding of acquired information in the central nervous system, according to Dr. Ungar. He calls these materials chemical code words of memory, which are analogous to the genetic code words that control heredity (C&EN, Nov. 3, 1969, page 4 3 ) . Whether these memory code words act by labeling the neural pathways or achieve the registration of experience in some other fashion, "the knowledge gotten will considerably enhance our understanding of the processing of information in the brain," says Dr. Ungar. From a pharmacological standpoint, the presence in the brain of substances such as this one points to the possibility of designing drugs with highly specific behavioral effects. Dr. Ungar proposes to call the tetradecapeptide "scotophobin" (from the Greek skotos = dark, and phobos — fear). It's isolated from brains of rats which have acquired a fear of the dark from being subjected to electric shock whenever they take refuge in the dark chamber of a three-compartment system. Activity of the material is confirmed by injecting untrained mice with brain extracts of trained rats. Brains of more than 3000 rats were used to get enough material. The Texas team homogenizes the brains and makes a crude RNA preparation from which the active material is dialyzed out at pH 3.7. The mixture obtained after these initial steps is submitted to gel filtration on Sephadex G 25 and is further fractionated using thin-layer chromatography. Using a microdansylation procedure (two-dimensional chromatography), the scientists find after acid hydrolysis the following amino acids: aspartic acid (ASP), asparagine (ASN), glutamic acid ( G L U ) , glutamine ( G L N ) , glycine (GLY), lysine (LYS), serine (SER), and tyrosine (TYR). The Nterminal group is serine.

Dr. W. C. Starbuck performed a quantitative amino acid analysis which yielded the composition amounts of each amino acid. After incubation with trypsin, two fragments (T x and T 2 ) were obtained. T1 contains GLY, GLU, GLN, ASN, ASP, SER, and LYS. T 2 contains GLY, GLN, SER, and TYR. The N-terminal group of both fragments is serine. Dr. Desiderio determined the sequence of the amino acids by highresolution mass spectrometry. The spectrum was taken on a CEC Model 21-110, which gives accurate masses of the fragments to ±0.003 mass unit. All possible sequential dipeptides along the chain were found. Although this determination has only been performed once, Dr. Desiderio stresses that the "compositions are so unique that there is a good probability that the sequence we've proposed is correct." The structure of the peptide will be confirmed by separate synthesis and tested for its behavioral effect, says Dr. Ungar, to determine if the peptide is the correct one.

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8 9 LYS "• SER

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I 6 GLN

I 7 GLY

1 10 GLN

1 13 GLN '

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14 TYR

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12 GLY

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11 GLY

i Connecticut's Daddario Response to home state

SCIENCE:

Losing a Friend Federally funded scientific research, already suffering from a general decline in popularity on Capitol Hill, could receive yet another heavy blow if Congressman Emilio Q. Daddario (D.-Conn.) responds to home state pressures and decides to run for governor or for a Senate seat in the 1970 elections. Speculation, active since the announcement shortly after the first of the year by Connecticut Gov. John Dempsey (D.) that he will not seek re-election, reached a peak last week as pressure mounted on the Congressman to make a decision by the middle of February. Rep. Daddario, currently serving his sixth term, is one of the scientific community's most effective Congressional spokesmen. A charter member of the House Committee on Science and Astronautics, he has chaired the important Science, Research, and Development Subcommittee since its establishment in 1963. During his tenure, Rep. Daddario has championed various reforms to make scientific information and "state of the art" knowledge readily available to members of Congress who must vote on science and technology policy questions, as well as on research funding. He is concerned with scientific approaches to pollution control and the need for what he calls "technological assessment." The Connecticut Congressman is also being touted as the leading contender for the seat held by Sen. Thomas Dodd who has fallen into disfavor with the state Democratic party. Rep. Daddario's departure would leave Rep. John Davis (D.-Ga.) as number one man on the subcommittee, but a final decision on his successor would be made by chairman George Miller of the full committee. FEB. 9, 1970 C&EN

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