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 Modified polypeptides with high activity and reduced allergenicity

Details
Inventors: Weisgerber, David J.; Rubingh, Donn N.;
Assignee: The Procter & Gamble Co. (Cincinnati, OH)
Primary Examiner: Page; Thurman K.
Assistant Examiner: Howard; S.
Attorney, Agent or Firm: Murphy; Stephen T., Kendall; Dara M., Tsuneki; Fumiko

The present invention relates to a modified polypeptide which has an enzymatic activity level of greater than about 70% of the parent polypeptide and an allergenic response level of less than about 33% of the parent polypeptide. Embodiments of the present invention relate to modified polypeptides with reduced allergenicity and high enzymatice activity comprising the formula: A-B.sub.n wherein A is an enzyme, and mixtures thereof; B is a twin polymer moiety, having a total molecular weight of from about 0.5 kilodaltons (KD) to about 40 KD, having the formula ##STR1## conjugated to the enzyme; wherein R.sub.1 and R.sub.2 are essentially straight chain polymers, having a molecular weight ranging from about 0.25 KD to about 20 KD; wherein the ratio of the molecular weights of R.sub.1 and R.sub.2 is from about 1:10 to about 10:1; wherein X is a linking moiety which links the twin moeity to a single site on the enzyme; and n is the number of twin polymer moietis conjugated to the enzyme, and represents an integer from about 1 to about 15.

DETAILED DESCRIPTION OF THE INVENTION The modified polypeptide of the present invention is represented by the formula: A-B.
sub.
n containing, as essential components, a enzyme, A, and a plurality, n, of twin polymer moieties, B.
While not intending to be limited by theory, it is believed that the conjugation of the twin polymer moieties to the enzyme provides a balanced stearic hindrance of the activated surface of the enzyme as to allow for high activity but simultaneously prevent stimulation of the immune system and subsequent antibody formation responsible for allergic reaction.
As used herein, the phrase "amino acid sequence" refers to a specific configuration of the amino acids comprising a polypeptide.
The following is a list of abbreviations used herein to describe amino acids:
Three-letter
Amino Acid Abbreviation One-letter Symbol
Alanine Ala A
Arginine Arg R
Asparagine Asn N
Aspartic Acid Asp D
Cysteine Cys C
Glutamine Gln Q
Glutamic Acid Glu Q
Glycine Gly G
Histidine His H
Isoleucine Ile I
Leucine Leu L
Lysine Lys K
Methionine Met M
Phenylalanine Phe F
Proline Pro P
Serine Ser S
Threonine Thr T
Tryptophan Trp W
Tyrosine Tyr Y
Valine Val V
No amino acid at position Xaa *
As used herein, the term "mutation" refers to the genetic alteration of an organism, which in turn alters the amino acid sequence of the enzyme produced by that organism



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