segunda-feira, 26 de setembro de 2016

Um homem, dois Nobel

O pioneiro na determinação da sequência de aminoácidos foi Frederick Sanger, agraciado com dois Prêmios Nobel em 1958 e 1980. Contudo, essa proposta era controversa, porque os vinte aminoácidos proteinogênicos eram conhecidos, mas muitos pesquisadores pensavam que as proteínas eram randômicas, conforme o obituário de Sanger, publicado no The Telegraph: “Thus, when Chibnall tried to get Sanger a grant from the Medical Research Council to work on protein structure, the grant was refused because “everyone knew” that the pattern of amino acids in a protein was random.”i . A primeira proteína escolhida foi a insulina, por ser relativamente pequena e disponível em quantidades significativas.
O método de Sanger consistia em marcar o aminoácido final e quebrar essa ligação peptídica. O processo era lento, mas a sequência de 51 aminoácidos ligados por duas pontes de dissulfeto foi determinada.
Contudo, muitos pesquisadores mantiveram seu ponto de vista com o objetivo de apontar a aleatoriedade da sequência dos aminoácidos. O bioquímico francês e Prêmio Nobel de 1965, Jacques Monod descreveu a descoberta de Sanger da seguinte forma:
The first description of a globular protein’s complete sequence was given by Sangar in 1952. It was both a revelation and a disappointment. This sequence, which one knew to define the structure, hence the elective properties of a functional protein (insulin), proved to be without any regularity, any special feature, any restrictive characteristic. Even so the hope remained that, with the gradual accumulation of other such findings, a few general laws of assembly as well as certain functional correlations would finally come to light. Today our information extends to hundreds of sequences corresponding to various proteins extracted from all sorts of organisms. From the work on these sequences, and after systematically comparing them with the help of modern means of analysis and computing,we are now in a position to deduce the general law: it is that of chance. To be more specific: these structures are “random”in the precise sense that, were we to know the exact order of 199 residues [i.e., amino acids] in a protein containing 200, it would be impossible to formulate any rule, theoretical or empirical, enabling us to predict the nature of the one residue not yet identified in the analysis.
To say that in a polypeptide the amino acid sequence is “random”may perhaps sound like a roundabout admission of ignorance. Quite to the contrary, the statement expresses the nature of the facts. [Chance and Necessity, Vintage Books Edition, 1972, 96] “



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