Beta-amino acids
Disclosed are β-amino acid monomers containing cylcoalkyl, cycloalkenyl, and heterocylic substituents which encompass the α and β carbons of the peptide backbone and β-polypeptides made from such monomers. Method of generating combinatorial libraries of polypeptides containing the β-peptide residues and libraries formed thereby are disclosed.
1. A composition comprising a polypeptide comprising the formula:
wherein Z is selected from the group consisting of:
and wherein each residue's X and Y combined, together with the carbon atoms to which they are bonded, independently define a substituted or unsubstituted C 3 -C 8 cycloalkyl, cycloalkenyl or heterocyclic ring having one or more nitrogen atoms as the sole heteroatom, the substituents being selected from the group consisting of hydroxy, linear or branched C 1 -C 6 -alkyl, alkenyl, alkynyl; hydroxy-C 1 -C 6 -alkyl, amino-C 1 -C 6 -alkyl, C 1 -C 6 -alkyloxy, C 1 -C 6 -alkyloxy-C 1 -C 6 -alkyl, amino, mono- or di-C 1 -C 6 -alkylamino, carboxamido, carboxamido C 1 -C 6 -alkyl, sulfonamido, sulfonamido-C 1 -C 6 -alkyl, urea, cyano, fluoro, thio, C 1 -C 6 -alkylthio, mono- or bicyclic aryl, mono- or bicyclic heteraryl having up to 5 heteroatoms selected from N, O, and S; mono- or bicyclic aryl-C 1 -C 6 -alkyl, and heteroaryl-C 1 -C 6 -alkyl;
or X and Y are independently selected from the group consisting of hydroxy, linear or branched C 1 -C 6 -alkyl, alkenyl, alkynyl; hydroxy-C 1 -C 6 -alkyl, amino-C 1 -C 6 -alkyloxy, C 1 -C 6 -alkyloxy-C 1 -C 6 -alkyl, amino, mono- or di-C 1 -C 6 -alkylamino, carboxamido, carboxamido-C 1 -C 6 -alkyl, sulfonamido, sulfonamido-C 1 -C 6 -alkyl, urea, cyano, fluoro, thio, C 1 -C 6 -alkylthio, mono- or bicyclic aryl, mono- or bicyclic heteraryl having up to 5 heteroatoms selected from N, O, and S; mono- or bicyclic aryl-C 1 -C 6 -alkyl, and heteroaryl-C 1 -C 6 -alkyl; and
wherein m is 1, and
wherein n and p are 1.
2. A composition comprising a polypeptide comprising the formula:
wherein Z is a single bond; and
each residue's X and Y combined, together with the carbon atoms to which they are bonded, independently define a substituted C 4 -C 6 cycloalkyl, cycloalkenyl, or heterocyclic ring having one nitrogen atom as the sole hetero atom;
wherein m is 1, and
wherein n and p are 1.
3. The composition of claim 2 , wherein X and Y combined, together with the carbon atoms to which they are bonded, independently define a substituted cyclopentyl, cyclohexyl, pyrrolidinyl, or piperidinyl ring.
4. The composition of claim 3 , wherein the substituent is selected from the group consisting of amino, mono- or di-C 1 -C 6 -alkylamino, carboxamido, sulfonamido, urea, thio, and C 1 -C 6 -alkylthio.
5. The composition of claim 2 , wherein X and Y combined, together with the carbon atoms to which they are bonded, independently define an amino-substituted cyclopentyl, amino-substituted cyclohexyl, amino-substituted pyrrolidinyl, or amino-substituted piperidinyl ring.
6. A composition comprising a polypeptide comprising the formula
wherein X and Y combined, together with the carbon atoms to which they are bonded, independently define a substituted C 3 -C 8 cycloalkyl, cycloalkenyl or heterocyclic ring having one or more nitrogen atoms as the sole heteroatom, the substituents being selected from the group consisting of hydroxy, linear or branched C 1 -C 6 -alkyl, alkenyl, alkynyl; hydroxy-C 1 -C 6 -alkyl, amino-C 1 -C 6 -alkyl, C 1 -C 6 -alkyloxy, C 1 -C 6 -alkyloxy-C 1 -C 6 -alkyl, amino, mono- or di-C 1 -C 6 -alkylamino, carboxamido, carboxamido-C 1 -C 6 -alkyl, sulfonamido, sulfonamido-C 1 -C 6 -alkyl, urea, cyano, fluoro, thio, C 1 -C 6 -alkylthio, mono- or bicyclic aryl, mono- or bicyclic heteraryl having up to 5 heteroatoms selected from N, O, and S; mono- or bicyclic aryl-C 1 -C 6 -alkyl, and heteroaryl-C 1 -C 6 -alkyl; and
n is a positive integer greater than 3.
7. The composition of claim 6 , wherein X and Y combined, together with the carbon atoms to which they are bonded, independently define a substituted C 4 -C 6 cycloalkyl, cycloalkenyl, or heterocyclic ring having one nitrogen atom as the sole hetero atom.
8. The composition of claim 6 , X and Y combined, together with the carbon atoms to which they are bonded, independently define a substituted cyclopentyl, cyclohexyl, pyrrolidinyl, or piperidinyl ring.
9. The composition of claim 6 , wherein X and Y combined, together with the carbon atoms to which they are bonded, independently define a substituted cyclopentyl, cyclohexyl, pyrrolidinyl, or piperidinyl ring, wherein the substituent is selected from the group consisting of amino, mono- or di-C 1 -C 6 -alkylamino, carboxamido, sulfonamido, urea, thio, and C 1 -C 6 -alkylthio.