Polypeptides containing γ-amino acids

An unnatural polypeptide compound selected from the group consisting of:

• wherein:
• each Y is independently variable and is selected from the group consisting of a single bond or
• wherein each R3 in Formula (ii) is independently variable and is selected from the group consisting of hydrogen, linear or branched C1-C6-alkyl, alkenyl, or alkynyl;
• mono- or bicyclic aryl, mono- or bicyclic heteroaryl having up to 5 heteroatoms selected from N, O, and S;
• mono- or bicyclic aryl-C1-C6-alkyl, and mono- or bicyclic heteroaryl-C1-C6-alkyl;
• each R4 in Formula (ii) is selected from the group of substituents as listed hereinbelow for R1;
• each X and each Z in Formula (i) is independently variable and is selected from the group consisting of γ-amino acid residues, provided that at least one of X or Z is a substituted or unsubstituted cyclically-constrained γ-amino acid residue independently selected from the group consisting of:
• wherein R in Formula (iii), together with the carbons to which it is attached, independently defines a substituted or unsubstituted C5 to C10 cycloalkyl, cycloalkenyl, or heterocycle moiety, the heterocycle moiety having 1, 2, or 3 heteroatoms selected from the group consisting of N, S, and O;
• and further wherein substituents on the cyclically-constrained γ-amino acid residue of Formula (iii) are independently selected from the group consisting of linear or branched C1-C6-alkyl, alkenyl, or alkynyl;
• mono- or bicyclic aryl, mono- or bicyclic heteroaryl having up to 5 heteroatoms selected from N, O, and S;
• mono- or bicyclic aryl-C1-C6-alkyl, mono- or bicyclic heteroaryl-C1-C6-alkyl, —(CH2)n+1—OR2, —(CH2)n+1—SR2, —(CH2)n+1—S(═O)—CH2—R2, —(CH2)n+1—S(═O)2—CH2—R2, —(CH2)n+1—NR2R2, —(CH2)n+1—NHC(═O)R2, —(CH2)n+1—NHS(═O)2—CH2—R2, —(CH2)n+1—O—(CH2)m—R1, —(CH2)n+1—S—(CH2)m—R1, —(CH2)n+1—S(═O)—(CH2)m—R1, —(CH2)n+1—S(═O)2—(CH2)m—R1, —(CH2)n+1—NH—(CH2)m—R1, —(CH2)n+1—N—{(CH2)m—R1}2, —(CH2)n+1—NHC(═O)—(CH2)n+1—R1, —(CH2)n+1—NHS(═O)2—(CH2)m—R1;
• —(CH2)n—OR, —(CH2)n—SR2, —(CH2)n—S(═O)—CH2—R2, —(CH2)n—S(═O)2—CH2—R2, —(CH2)n—NR2R2, —(CH2)n—NHC(═O)R2, —(CH2)n—NHS(═O)2—CH2—R2, —(CH2)n—O—(CH2)m—R1, —(CH2)n—S—(CH2)m—R1, —(CH2)n—S(═O)—(CH2)m—R1, —(CH2)n—S(═O)2—(CH2)m—R1, —(CH2)n—NH—(CH2)m—R1, —(CH2)n—N—{(CH2)m—R1}2, —(CH2)n—NHC(═O)—(CH2)m—R1, and —(CH2)n—NHS(═O)2—(CH2)m—R1;
• wherein R2 is independently selected from the group consisting of hydrogen, C1-C6-alkyl, alkenyl, or alkynyl;
• mono- or bicyclic aryl, mono- or bicyclic heteroaryl having up to 5 heteroatoms selected from N, O, and S;
• mono- or bicyclic aryl-C1-C6-alkyl, and mono- or bicyclic heteroaryl-C1-C6-alkyl;
• and wherein R1 is selected from the group consisting of hydroxy, C1-C6-alkyloxy, aryloxy, heteroaryloxy, thio, C1-C6-alkylthio, C1-C6-alkylsulfinyl, C1-C6-alkylsulfonyl, arylthio, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, amino, mono- or di-C1-C6-alkylamino, mono- or diarylamino, mono- or diheteroarylamino, N-alkyl-N-arylamino, N-alkyl-N-heteroarylamino, N-aryl-N-heteroarylamino, aryl-C1-C6-alkylamino, carboxylic acid, carboxamide, mono- or di-C1-C6-alkylcarboxamide, mono- or diarylcarboxamide, mono- or diheteroarylcarboxamide, N-alkyl-N-arylcarboxamide, N-alkyl-N-heteroarylcarboxamide, N-aryl-N-heteroarylcarboxamide, sulfonic acid, sulfonamide, mono- or di-C1-C6-alkylsulfonamide, mono- or diarylsulfonamide, mono- or diheteroarylsulfonamide, N-alkyl-N-arylsulfonamide, N-alkyl-N-heteroarylsulfonamide, N-aryl-N-heteroarylsulfonamide, urea;
• and mono- di- or tri-substituted urea, wherein the subsitutent(s) is selected from the group consisting of C1-C6-alkyl, aryl, heteroaryl;
• O-alkylurethane, O-arylurethane, and O-heteroarylurethane, and wherein m is an integer of from 2-6 and n is an integer of from 0-6;
• wherein each “A” of Formula (i) is independently selected from the group consisting of hydrogen, hydroxy, an amino-terminus protecting group, and a carboxy-terminus protecting group;
• wherein each of “a,” “c,” and “d” is an independently variable positive integer;
• and
• salts thereof.