Naidu, Claudia

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South African Medical JournalSuid-Afrikaanse Tydskrif vir GeneeskundeVAN DIE REDAKSIEPEPTIED-A TIBIOTIKAParallel met ondersoek na die struktuur van die poli-peptiedprinsipes van die harsingslymklier,l vindnavorsing op 'n soortgelyke grondslag plaas om diestruktuur van die polipeptied-antibiotika2 vas te ste!.Tirotrisien, die eerste bakteriese antibiotika watverkry was (van Bacillus brevis), is naderhand ingramisidiene en tirosidiene geskei. Daar is getoon dateen hiervan, gramisidien-S, uit 10 aminosuur-eenhedebestaan, en die wyse waarop hulle aaneenskakel, isbekend. Daar is twee molekule elk van l-ornitien,I-valien, I-Ieusien, I-prolien en d-fenielalanien. Dievolledige struktuur van hierdie antibiotika word as volgbeskrywe./Iorn~I Val I LeuI II Pro d PheI Id Phe I ProI II Leu 1Val~IOrn/Die struktuur van tirosidien-A en tirosidien-B is ookbekend en toon 'n groot ooreenkoms met die vangramisidien-S.' Hulle is almal ringvormige dekapeptiede,met 5 van die aminosure, in elk, identies en in dieselfdevolgorde aaneengeskake!. Elkeen bevat d-fenielalanienen nie die l-isomeer nje wat gewoonlik in proteleneaanwesig is. Dit is aan die handgedoen dat hierdieeienskap miskien die antibakteriese aktiwiteit vanhierdie besondere polipeptied-antibiotika verklaar. Dieringvorrnige aard van die polipeptiede is nie noodsaaklikvir antibakteriese aktiwiteit nie, aangesien 'n reguit-ketting-dekapeptied, met dieselfde aminosuur-volgorde,gesintetiseerd is, wat l/lOde tot lj40ste van die anti-bakteriese aktiwiteit van gramisidien-S3besit. Tirosidieneen gramisidien-S is ietwat meer ingewikkeld in struktuuras die oktapeptiede vasopressien en oksitosien.Dit kom voor asof die verskillende antibiotika watdeur Bacillus subtilis geproduseer word, ook polipeptiedeis. Dit is bewys dat basitrasien byvoorbeeJd, uit10 verskillende polipeptiede bestaan, waarvan 3 anti-bakteries is. Die volledige struktuur van basitrasien-Ais nog nie vasgestel nie maar die aminosuur-volgordevan- 'n gedeelte van die molekuul is bekend.1 September 1956EDITORIALPEPTIDE A TIBIOTICSParallel with the investigations into the structure of thepolypeptide principles of the pituitary gland,! work hasbeen proceeding along similar lines to determine theconstitution of the polypeptide antibiotics.2Tyrothricin, the first bacterial antibiotic to be ob-tained (from Bacillus brevis) was separated subse-quently into gramicidins and tyrocidines. One of these,gramicidin S, has been shown to consist of 10 amino-acid units, and the way in which they are linked togetheris known. There are 2 molecules each of I-ornithine,I-valine, I-leucine, I-proline and d-phenylalanine. Thecomplete structure of this antibiotic is depicted asfollows:/IOrn~I Val I LeuI II Pro d PheI Id Phe I ProI I_1 Leu I Val~IOrn/The structure of tyrocidine A and tyrocidine B isalso known, and closely resembles that of gramicidin S.They are all cyclic decapeptides, with 5 of the amino'acids in each identical and linked together in the samesequence.... Each contains d-phenylalanine, not theI isomer, which is commonly present in proteins. Ithas been suggested that this feature may accountfor the antibacterial activity of these particular poly-peptide antibiotics. The cyclic nature of the poly-peptides is not essential for antibacterial activity, sincea straight-chain decapeptide with the same amino-acidsequence has been synthesized and found to have1ll0th to 1/40th the antibacterial activity of grami-cidin S.3 The tyrocidines and gramicidin S are some-what more complicated in structure than the- octa-peptides vasopressin and oxytocin.The several antibiotics produced by Bacillus subtilisappear also to be polypeptides. Bacitracin, for example,has been shown to consist of 10 different polypeptides,of which 3 have antibacterial potency. The completestructure of bacitracin A is not yet established, but theamino-acid sequence of part of the molecule is known.The group of peptide antibiotics obtained from831832 S.A.' MEDICAL JOURNAL 1 September 1956Die peptied-antibiotika-groep wat van Bacillus subtilisverkry word, staan as polimiksiene bekend. Hullestruktuur is gedeeItelik gestaaf. Dit is getoon datpolimiksien 5 bestanddele het waarvan die vernaamsteeen, polimiksien-A, identies met erosporien is.Die samestelling van ander peptiede met antibiotieseaktiwiteit word ondersoek, terwyl die sintese van sulkemiddele soos die reguitketting-dekapeptied, waarnahierbo verwys is, van groot belang is.Slegs gedurende die afgelope paar jare is die pogings,om die struktuur van die polipeptiede toe te Jig, geslaagd.Die metode van papierchromatografie eerder as dieouer tegnieke, het gehelp om die konstituerende amino-sure makliker te skei. Verder, deur gebruik te maak vanverwante metodes van navorsing, kan die volgorde vandie aminosure in die ketting vasgestel word, asook huIleaard en die relatiewe getalle van elk wat in die verbindingaangetref word. Met sommige van die metodes wat inhierdie studies gebruik is, word die. end-aminosuuruitgeken; sekere van hierdie metodes stel navorsers instaat om die polipeptied trapsgewyse af te breek. Deurmiddel van papierchromatografie is die produkte vanparsiele hidrolise van volledige polipeptied-antibiotikaal van mekaar geskei; die kolletjies op die papier wordafsonderlik ge-eludeer, dan word die di- en tripeptiedeheeItemal crehidroliseer en die aminosure word deurverdere pa;ierchromatografie2 geldentifiseer. Waar diepoIipeptied by ondersoek nie vry is van yeptied-onsuiwerhede nie, moet ander metodes gebrUlk word.Een van die metodes wat vandag algemeen gebruik wordom die polipeptiede van mekaar te skei, is die vanteenstroomverdeling: die mengsel word agtereenvolgensin 'n spesiale apparaat verdeel wat 'n oplossings-vloeistof-fase en 'n waterfase bevat; daar is 'n aantalbuise so gerabgskik dat komponente m~t 'n hoe oplos-middeljwater-verdelingskoeffisient by d1e een en tvandie apparaat bymekaar kom en die met 'n lae verdeIings-koeffisient by die ander ent. Tirotrisien was deur hierdiemetode in verskeie verwante polipeptiede gefraksioneer.Papierelektroforese is nog 'n metode wat gebru.ik wordom verwante polipeptiede van mekaar te skel.Deur crebruik te maak van die nuwer en meer aantrek-like tegnieke wat dit moontIik maak om stowwe te skeien te ontleed sonder om hulIe unieke en labiele strukturete versteur, het navorsing i.v.m. polipeptiede die afgelopejare vinnig gevorder.1. Van die Redaksie (1955): S. Afr. T. Gen esk., 29,697.2. Robinson, F. A. (1956): J. Pharm. Pharmacol., 8, 297.3. Erlanger, B. Fen Goode, L (1934): 'ature, 174. 840.Bacillus polymyxa are ~own as polymy~ns. Theirstructure is partly established. Pol.ymyxIn ha.s beenshown to have 5 constituents, of which the mam one,polymyxin A, is identical with aerosporin,The structure of other peptides -having antibioticactivity is being investigated, while the .synthesis . ofsuch agents as the straight-chain decapeptlde to whichreference is made above, is of great interest.It is only in the last few years that attempts to eluci-date the structure of pcilypeptides have been successful.The method of paper chromatography has enabled t~econstituent amino-acids to be separated more eas1lythan by the older techniques. Furthermore, by the useof related methods of investigation the sequence ofthe amino acids in the chain can be determined, aswell as their nature and the relative numbers of eachpresent in the compound. ~ong the ~etho~s thathave been used in these stud1es are some III Wh1Ch theterminal amino-acid is identified; certain of the methodspermit stepwise degradation of the polypeptide to beeffected. By paper chromatography th~ prodl;lc~s .ofpartial hydrolysis of complete polypeptlde antlbIOtlcshave been separated from one another; the spots onthe paper are separately eluted, the di- and tTI.- pepti~esthen hydrolysed completely, and the ammo aC1dsidentified by further paper chromatography.2 Wherethe polypeptide under investigation is not free frompeptide impurities other .methods must be employed.One that is widely used at present, to separate poly-peptides from one another, is the metho~ of cou?ter-current distribution, in which the mixture 1S success1velypartitioned in a special apparatus containing a solventphase and an aqueous phase; there are a number oftubes so arranged that components with a higher solventwater partition-coefficient collect at o?~ end of .theaoparatus and those with a low partltIOn-coefficIentaccumulate at the other end. By this method tyro-thricin was fractionated into several related poly-peptides. Paper electrophoresis is another method usedto separate related polypeptides from one another.The investigation of polypeptides has advancedrapidly in recent years throu~h the appl.ication. of thenewer elegant techniques which make 1t poss1ble toseparate and analyse substances without disturbingtheir unique and labile structures.1. Editorial (1955): S. Afr. Med. J., 29, 697.2. Robinson, F A. (1956): J. Pharm. Pharmacal., 8, 297.3. Erlanger, B. F. and Goode, L (1954): Tature, 174, 840.BOOKS RECEIVED: BOEKE O. ITVANGAnnual Epidemiological and Vital Statistic~, 1953. Pp. 572. £2 IOsGeneva: World Health OrgamzatIOn. BJimgual edltlo,n(French and English). Local sales agent: Van Schalk sBookstore (Pty.), Pretoria. 1956. . .Composting: Sanitary Disposal and Reclamation of OrgamcWastes. By Harold B. Gotaas. Pp. 205, 49 figures. £1 5s.(French edition in preparation.) Geneva: Wor.ld HealthOrganization. 1956. Local sales agent: Van Schalk's Book-store (Ply.) Ltd., P.O. Box 724, Pretoria.. _Expert Committee on Trachoma, Second Report. No: 106. Pp.20.Is. 9d. Available also in French and Spamsh. Geneva:World Health Organization. 1956. Local Sales Agent:Van Schaik's Bookstore (pry.) Ltd., P.O. Box 724, Pretona.Ciba Foundation Colloquia on Endocrinology. Volume 9. InTernalSecreTions of the Pancreas. By G. E. W. Wolstenholme,O.B.E., M.A., M.B., B.Ch. and Cecilia M. O'Connor, B.Sc.Pp. xii + 292, 100 illustrations. 40s. London: J. & A. Churc-hill Ltd. 1956.,Recent Advances in Pharmacology. Second EdiTion. J. M. Robson,M.D., D.Sc., FR.S.E. and C. A. Keele, M.D., FR.C.P.(Land.). Pp. xii + 501, 66 illustrations. 4Os. London:J. & A. Churchill Ltd. 1956.•

Editorial: Peptide Antibiotics

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Editorial: Peptide Antibiotics

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