The total chemical synthesis of RNase A using modern chemical ligation methods is described, illustrating the significant advances that have been made in chemical protein synthesis since Gutte and Merrifield's pioneering preparation of RNase A in 1969. The identity of the synthetic product was confirmed through rigorous characterization, including the determination of the X-ray crystal structure to 1.1 Angstrom resolution. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 90:278–286, 2008.
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