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] “
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] “
ihttp://www.telegraph.co.uk/news/obituaries/science-obituaries/10462574/Frederick-Sanger-OM.html,
acessado em 27 de junho de 2016
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