Amide bond formation is one of the most important reactions in both chemistry and biology(1-4), but there is currently no chemical method of achieving alpha-peptide ligation in water that tolerates all of the 20 proteinogenic amino acids at the peptide ligation site. The universal genetic code establishes that the biological role of peptides predates life's last universal common ancestor and that peptides played an essential part in the origins of life(5-9). The essential role of sulfur in the citric acid cycle, non-ribosomal peptide synthesis and polyketide biosynthesis point towards thioester-dependent peptide ligations preceding RNA-dependent protein synthesis during the evolution of life(5,9-13). However, a robust mechanism for aminoacyl thioester formation has not been demonstrated(13). Here we report a chemoselective, high-yielding alpha-aminonitrile ligation that exploits only prebiotically plausible molecules-hydrogen sulfide, thioacetate(12,14) and ferricyanide(12,14-17) or cyanoacetylene(8,14)-to yield alpha-peptides in water. The ligation is extremely selective for alpha-aminonitrile coupling and tolerates all of the 20 proteinogenic amino acid residues. Two essential features enable peptide ligation in water: the reactivity and pKaH of alpha-aminonitriles makes them compatible with ligation at neutral pH and N-acylation stabilizes the peptide product and activates the peptide precursor to (biomimetic) N-to-C peptide ligation. Our model unites prebiotic aminonitrile synthesis and biological alpha-peptides, suggesting that short N-acyl peptide nitriles were plausible substrates during early evolution.