| 摘要 |
<p>The subject invention provides for a process for making a mixture of acetate salts of polypeptides, each of which consisting of glutamic acid, alanine, tyrosine and lysine, wherein the mixture has a desired peak molecular weight, comprising: a) polymerizing N-carboxyanhydrides of tyrosine, alanine, gamma-benzyl glutamate and trifluoroacetyllysine with an initiator in an amount of 0.01% to 20% by weight for a suitable period of time and at a suitable temperature to form a mixture of protected polypeptides, which mixture of polypeptides in unprotected form having a first peak molecular weight; b) removing the benzyl protecting group from the mixture of protected polypeptides by contacting the polypeptides with a hydrogenolysis catalyst and hydrogen to produce a mixture of trifluoroacetyl protected polypeptides, which mixture of polypeptides in unprotected form having the first peak molecular weight; c) removing the trifluoroacetyl protecting group from the trifluoroacetyl protected polypeptides by contacting the polypeptides with an organic base solution to form a mixture of polypeptides, which mixtures of polypeptides in unprotected form having the first peak molecular weight; d) removing the free trifluoroacetyl groups and low molecular weight impurities by ultrafiltration to obtain the mixture of polypeptides each of which consisting of glutamic acid, alanine, tyrosine and lysine; and e) contacting the mixture of polypeptides each of which consisting of glutamic acid, alanine, tyrosine and lysine with an aqueous solution of acetic acid to form the mixture of acetate salts of polypeptides each of which consisting of glutamic acid, alanine, tyrosine and lysine and having the desired peak molecular weight.</p> |
