March 29, 1906] 



NA TURE 



5i9 



Experiments are being Carried out for the purpose of 

 discovering some good substitute for glass in mirror 

 making. " Invar " has proved to be too soft, and the 

 fused quartz discs have not been a success. Prof. Hale 

 suggests that speculum metal will be found to answer the 

 purpose better than glass. 



Photographs taken with the Snow telescope have proved 

 belter than those obtained with the 40-inch refractor at 

 Verkes, and Prof. Hale states that, from a mechanical 

 standpoint also, the telescope has proved completely 

 successful. 



STUDIES OX THE SYNTHESIS OF PEPTIDES 



AND PROTEIDS. 1 

 A MONG the many brilliant achievements in synthetic 

 ■^* chemistry accomplished by Prof. Emil Fischer during 

 the last quarter of a century, none have surpassed in 

 interest the remarkable series of researches which formed 

 the subject of a recent address to the German Chemical 

 Society. 



In reading this address it is impossible to say which 

 commands greater admiration, the author's consummate 

 skill and endless resource in sweeping aside each difficulty 

 as it arose in a most intricate field of experimental 

 inquiry, or his intense and ceaseless activity in producing 

 almost month by month during the past five years a wealth 

 of new knowledge of the very first importance to biological 

 science. 



" Whilst our cautious colleagues," says Prof. Fischer, 

 " fear that a systematic study of this group of compounds 

 (the proteids) will be beset with endless difficulties on 

 account of their troublesome physical features, there are 

 others, among whom I count myself, who are more 

 optimistic, and hold that an attempt at least ought to be 

 made with every modern appliance to lay siege to this 

 unconquered citadel ; for it is only by a bold attempt that 

 the limitations of our present methods can be adequately 

 gauged." 



The success which has so far attended Prof. Fischer's 

 t'ust attack promises a speedy capitulation. The proteids 

 will then be made to deliver up the key to their molecular 

 structure, and the first real advance in biochemistry will 

 have been accomplished. 



Although physiological chemistry has done much in the 

 past in the way of classifying the numerous members of the 

 proteid group, in preparing a few members in the crystal- 

 line form, in attaching to different individuals different 

 biological functions, and in ascertaining the fundamental 

 changes effected by ferment action, our knowledge of their 

 chemical constitution has up to the present been extremely 

 meagre. Apart from the percentage composition, it is 

 limited mainly to the results of hydrolysis by acids, alkalis, 

 or digestive ferments. When submitted to these agents 

 all proteids yield successively albumoses, peptones, and, 

 finally, amino-acids. Of the nature of the first two we 

 are but little better informed than of that of the proteids 

 themselves. 



The study of the amino-acids has been attended with 

 more success, for not only has the structure of the majority 

 of them been ascertained, but many have been prepared 

 synthetically. The following is a list of amino-acids 

 obtained by hydrolvsing one or other of the natural 

 proteids : — 



Glycine 



Alanine 



Aminovaleric acid 



Leucine 



Isoleucine 



Phenylalanine 



Glutamic acid 



Aspartic acid 



Cysteine 



a-Pyrrolidine carboxylic acid 

 (proline) 



Hydroxy-pyrrolidine carb- 

 oxylic acid (oxypyroline) 



Serine (n-amino-/3-hydroxy- 

 propionic acid) 



Tyrosine 



Tryptophane (skatolamino- 

 acetic acid) 



Lysine 



Arginine 



Histidine 



Diaminotrihydroxydodecanic 

 acid 



Diaminoglutaric acid 



Diaminoadipic acid 



Hvdroxyaminosuccinic acid 



Dihydroxyaminosuberic acid 



Vide Address by Prof. Emil Fischer, " Untersuchungen liber Amino- 

 en Polypeptide und Proteine " (/>V.w. '.,v .:.'■ Antscken Ckem. G, tell., 

 , xxxix., 530.) 



NO. I9OO, VOL. J 3] 



It was to the study of these acids — the fragments, so 

 to speak, of the albumin molecule — that Fischer first 

 directed his attention, hoping ultimately by piecing them 

 together to construct the simplest of the albumins. In 

 the synthesis of the monoamino-acids Fischer has added 

 to the methods already known that of brominating the 

 alkyl malonic esters and then converting the correspond- 

 ing acid into the a-bromo-fatty acid, which with ammonia 

 viefds the amino-acid. He has, moreover, devised an 

 ingenious process for resolving the synthetic, and, con- 

 sequently, inactive compounds into their active components. 

 The amino-acids are such weak acids that they refuse to 

 form crystalline salts with the active alkaloids. By con- 

 verting them into the benzoyl or formyl derivatives, strong 

 acids are produced which may be easily resolved by the 

 ordinary process of fractionally crystallising the salts of 

 the active bases. The diamino-acids, such as ornithine 

 (a5-diaminovaleric acid) and lysine (ae-diaminocaproic 

 acid), both common products (the former as arginine) of 

 proteid hydrolysis, have also been synthesised by Fischer 

 by adapting Gabriel's reaction in one case and that of 

 Blank in the other. Gabriel's phthalimidopropylmalonic 

 ester, when brominated, gives a monobromo-derivative, 

 which is then hydrolysed and heated to remove one carboxyl 

 group, the resulting compound being phthalimidobromo- 

 valeric acid, 



.CO, 

 C,II 4 N.CH.,.CH.,.CIL CHBr.COOH. 



v co x 



This was converted into the amino-derivative, and by 

 splitting off the phthalyl radical the racemic form of 

 natural ornithine was obtained, 



NH.,CH„.CH. 2 .CH.,CH(NH„).COOH. 

 The starting point for the preparation of lysine was 

 Blank's 7-cyanopropylmalonic ester, 



CN.CH 2 .CH 2 .CH. 2 .CH(COOC 2 H 5 ) 2 , 

 which is converted by nitrous acid into a-oximino-5-cyano- 

 valeric ester, 



CN.CH 2 .CH 2 .CH 2 C(:NOH).COOC 2 H 5 . 

 The latter, on reduction, yields the racemic form of lysine 

 (ae-diaminocaproic acid). The synthesis of hydroxyamino- 

 acids such as serine of silk fibroin has also been accom- 

 plished by applying Strecker's reaction to the hydroxy- 

 aldehvdes. Thus ammonia converts the cyanhydrin oi 

 glycollic aldehyde into the aminocyanhydrin which on 

 hydrolysis yields inactive serine, 



CH„(OH).CHO— CH s (OH).CH(OH).CN— 



CH,(OH).CHNH.,.CN— CH.,(OH).CHNH 2 .COOH. 



Of no less importance to the solution of the albumin 

 problem have been the new methods furnished by Fischer 

 for the separation and identification of the products of 

 proteid hydrolysis, for a correct knowledge of the varied 

 compounds which compose the albumin molecule must 

 necessarily precede any attempt to effect its synthesis. 

 Foremost among these stands the "ester method." It 

 consists in converting the mixture of amino-acids, obtained 

 on hydrolysis, into the corresponding esters, which are 

 then submitted to fractional distillation under very much 

 reduced pressure (10-15 mm.). The method cannot, how- 

 ever, be conveniently applied to the separation of tyrosine 

 or the diamino-acids, yvhich are treated in a different 

 fashion. Space does not permit of more than a passing 

 reference to the formation of benzoyl, formyl, and 

 0-naphthalene sulphonyl derivatives, and of the phenyl 

 hydantoins obtained with phenylisocyanate, all of which 

 have been utilised either in the purification or identifi- 

 cation of the amino-acids. We must leave this part of 

 the subject in order to follow Prof. Fischer into the more 

 attractive field of constructive research, and examine the 

 plans which he has laid for attacking the synthetic side 

 of the problem. Simply stated, the object he has had in 

 view has been to link "together two, three, four, or more 

 molecules of those amino-acids which the proteids yield 

 on hydrolysis, and by varying the combinations to 

 obtain' eventually something resembling the peptones or 

 the simplest albumins. To these artificial combinations of 



