Peptides without amino acids

Schematic ball and stick model of aminoacetonitrile molecule, a compound containing both nitrile and amine groups. (Colour code: Carbon, C: black; Hydrogen, H: white; Nitrogen, N: blue)

PEPTIDES, one of the fundamental building blocks of life, can be formed from the primitive precursors of amino acids under conditions similar to those expected on the primordial earth, finds a new University College London (UCL) study. The findings, published in “Nature”, could be a missing piece of the puzzle of how life first formed. “Peptides, which are chains of amino acids, are an absolutely essential element of all life on earth…. but they themselves require enzymes to control their formation from amino acids,” explained the study's lead author, Matthew Powner. “So we've had a classic chicken-and-egg problem—how were the first enzymes made?”

Powner’s team has demonstrated that the precursors to amino acids, called aminonitriles, can be easily and selectively turned into peptides in water, taking advantage of their own built-in reactivity with the help of other molecules that were present in primordial environments.  “Many researchers have sought to understand how peptides first formed to help life develop, but almost all of the research has focussed on amino acids,” said Powner. Aminonitriles require harsh conditions, typically strongly acidic or alkaline, to form amino acids. Then amino acids must be recharged with energy to make peptides. The researchers found a way to bypass both of these steps, making peptides from energy-rich aminonitriles.

They found that aminonitriles have the innate reactivity to achieve peptide bond formation in water with greater ease than amino acids. The team identified a sequence of simple reactions, combining hydrogen sulfide with aminonitriles and another chemical substrate ferricyanide, to yield peptides. “Controlled synthesis, in response to environmental or internal stimuli, is an essential element of metabolic regulation, so we think that peptide synthesis could have been part of a natural cycle that took place in the very early evolution of life,” said Pierre Canavelli, the first author of the study.

"This is the first time that peptides have been convincingly shown to form without using amino acids in water, using relatively gentle conditions likely to be available on the primitive earth," said co-author Saidul Islam.