Methods for forming peptides and peptide conjugates and peptides and peptide conjugates compositions formed thereby
AssigneeThe University of Toledo
InventorsSteven J. Sucheck, Rommel S. Talan, Partha Karmakar
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Abstract
Methods for building peptide chains containing sulfonyl modified amines at the N-terminus, or, within amino acid side chains, of a growing peptide in a solid-phase peptide synthesis are described. Further, compositions having a sulfonyl modified amine attached to the N-terminus, or within an amino acid side chain, of a polypeptide containing three or more amino acid residues are described.
Claims26
A peptide or peptide conjugate formed by a method of attaching amino acids to a growing peptide having an N-terminus using a solid-phase or a fluorous support, wherein the method comprises:
- attaching at least one sulfonamide group directly to the N-terminus of the growing peptide;
- and
- ligating the N-terminus with a peptidyl thio acid to produce a peptide or peptide conjugate, wherein the at least one sulfonamide group is removed during the ligation.
A method for synthesizing a peptide or peptide conjugate, comprising:
- attaching a 2,4-dinitrobenzenesulfonamide (dNBS) group or other sulfonamide group directly to an N-terminus of a growing peptide on a resin or a fluorous tag without the need to synthesize dNBS or other sulfonamide-modified amino acids or peptides;
- attaching a 2,4-dinitrobenzenesulfonamide (dNBS) group or other sulfonamide group site specifically to any position of an amino acid side chain during a solid-phase peptide synthesis;
- or a combination thereof.
A 2,4-dinitrobenzenesulfonamide (dNBS)-modified peptide formed by:
- attaching a 2,4-dinitrobenzenesulfonamide (dNBS) group directly to an N-terminus of a growing peptide on a resin or a fluorous tag without synthesizing dNBS-modified amino acids or peptides;
- attaching a 2,4-dinitrobenzenesulfonamide (dNBS) group site-specifically to any position of an amino acid side chain during a solid-phase peptide synthesis;
- or a combination thereof.
A compound having the formula III:
- wherein
- A is a solid-phase or fluorous support, or a linker grafted to a solid-phase or fluorous support or hydrogen;
- X is O, OH, NH, NH2, NR1, or NHR1, wherein R1 is independently a hydrogen, C1-n alkyl, C1-n alkoxyl, or aryl-substituted C1-n alkyl;
- AA is an optimally protected amino acid or optimally protected peptide, or
- AA is an unprotected amino acid or unprotected peptide;
- n is a positive integer;
- R2 represents any optimally protected or unprotected natural or unnatural amino acid side chain, the side chain containing a sulfonamide moiety selected from:
- wherein, in R2, Z is independently NO2, CF3, —COR, or F;
- R is NH2, C1-n alkyl, or other electron withdrawing group;
- R3 is C1-n alkyl, or aryl-substituted C1-n alkyl;
- and, N is part of a primary or secondary sulfonamide;
- wherein, R4 represents an amine protecting group orthogonal to the bond between X and A, hydrogen, or moiety:
- wherein, in R4, Z is independently NO2, CF3, —COR, or F;
- R is NH2, C1-n alkyl, or other electron withdrawing group;
- and R3 is C1-n alkyl, or aryl-substituted C1-n alkyl;
- and wherein either:
- (i) n is an integer between one and fifty, or
- (ii) AA is an unprotected amino acid.
A compound selected from the group consisting of:
- dNBS-Alanine;
- dNBS-Ser-Ala-OH;
- dNBS-Val-Thr-Ser-Ala-OH (SEQ ID NO:
- 1);
- dNBS-Gly-Val-Thr-Ser-Ala-OH (SEQ ID NO:
- 2);
- dNBS-Gly-Val-(Ac3-Tn-α-Thr)-Ser-Ala-OH (SEQ ID NO:
- 3);
- N-α-Fmoc-N-im-Trityl-Protected L-Histidine Trityl Thioester;
- Fmoc-Pro-Ala-SH;
- N-Fmoc-His-Gly-Val-(Ac3-Tn-α-Thr)-Ser-Ala-OH (SEQ ID NO:
- 4);
- and
- Fmoc-Pro-Ala-His-Gly-Val-(Ac3-Tn-α-Thr)-Ser-Ala-OH (SEQ ID NO:
- 5).
A compound comprising dNBS-His-Gly-Val-(Ac3-Tn-α-Thr)-Ser-Ala-OH (SEQ ID NO:
- 6).
Dependencies are inferred from the claim text.