Calixarene-based peptide conformation mimetics, methods of use, and methods of making
A class of topomimetic calixarene-based peptide mimetics is described. Calixarene-based peptide mimetics have various biological activities such as, for example, bactericidal activity, antiangiogenic activity, and/or antitumor activity. Methods of use and methods of designing calixarene-based peptide mimetics are described.
1. A method for inhibiting bacterial infection and/or endotoxemia, the method comprising contacting bacterial cells with a calixarene-based peptide mimetic in an amount effective to kill the bacteria, and/or to neutralize endotoxin, wherein the calixarene-based peptide mimetic comprises
Compound 46 having the formula
Compound 36 having the formula
Compound 41 having the formula
Compound 4 having the formula
Compound 17 having the formula
Compound 3 having the formula
Compound 11a having the formula
Compound 39 having the formula
Compound 12 having the formula
Compound 21 having the formula
and
Compound 42 having the formula
wherein R═(CH 2 ) 4 NHC(═NH)NH 2 ;
or an isomer, tautomer, salt, solvate, or polymorph.
2. The method of claim 1 , wherein the calixarene-based peptide mimetic is provided as a phatmaceutically acceptable salt.
3. The method of claim 1 , wherein the calixarene-based peptide mimetic comprises an ionic form that is positively charged.
4. The method of claim 1 , wherein the contacting step occurs in vitro.
5. The method of claim 1 , wherein the contacting step occurs in vivo.
6. The method of claim 1 , wherein the calixarene-based peptide mimetic comprises the full cone conformer of compound 46 (compound 46a), the partial cone conformer of compound 46 (compound 46b), or an isomer, tautomer, salt, solvate, or polymorph thereof.
7. The method of claim 1 , wherein the isomer is a diastereomer or enantiomer.
8. A calixarene-based peptide mimetic, wherein the calixarene-based peptide mimetic is selected from the group consisting of
Compound 46 having the formula
Compound 36 having the formula
Compound 41 having the formula
Compound 4 having the formula
Compound 17 having the formula
Compound 3 having the formula
Compound 11a having the formula
Compound 39 having the formula
Compound 12 having the formula
Compound 21 having the formula
and
Compound 42 having the formula
wherein R═(CH 2 ) 4 NHC(═NH)NH 2 ;
or an isomer, tautomer, salt, solvate, or polymorph thereof.
9. The calixarene-based peptide mimetic of claim 8 , wherein the calixarene-based peptide mimetic comprises the full cone conformer of compound 46 (compound 46a), the partial cone conformer of compound 46 (compound 46b), or an isomer, tautomer, salt, solvate, or polymorph.
10. The calixarene-based peptide mimetic of claim 9 , wherein the isomer is a diastereomer or enantiomer.
11. A composition comprising a calixarene-based peptide mimetic of claim 8 .
12. The composition of claim 11 further comprising a pharmaceutically acceptable carrier.
13. The calixarene-based peptide mimetic of claim 8 , wherein the calixarene-based peptide mimetic comprises compound 36 or an isomer, tautomer, salt, solvate, or polymorph thereof.
14. The calixarene-based peptide mimetic of claim 8 , wherein the calixarene-based peptide mimetic comprises compound 41 or an isomer, tautomer, salt, solvate, or polymorph thereof.
15. The calixarene-based peptide mimetic of claim 8 , wherein the calixarene-based peptide mimetic comprises compound 4 or an isomer, tautomer, salt, solvate, or polymorph thereof.
16. The calixarene-based peptide mimetic of claim 8 , wherein the calixarene-based peptide mimetic comprises compound 17 or an isomer, tautomer, salt, solvate, or polymorph thereof.
17. The calixarene-based peptide mimetic of claim 8 , wherein the calixarene-based peptide mimetic comprises compound 3 or an isomer, tautomer, salt, solvate, or polymorph thereof.
18. The calixarene-based peptide mimetic of claim 8 , wherein the calixarene-based peptide mimetic comprises compound 11a or an isomer, tautomer, salt, solvate, or polymorph thereof.
19. The calixarene-based peptide mimetic of claim 8 , wherein the calixarene-based peptide mimetic comprises compound 39 or an isomer, tautomer, salt, solvate, or polymorph thereof.
20. The calixarene-based peptide mimetic of claim 8 , wherein the calixarene-based peptide mimetic comprises compound 12 or an isomer, tautomer, salt, solvate, or polymorph thereof.
21. The calixarene-based peptide mimetic of claim 8 , wherein the calixarene-based peptide mimetic comprises compound 21 or an isomer, tautomer, salt, solvate, or polymorph thereof.
22. The calixarene-based peptide mimetic of claim 8 , wherein the calixarene-based peptide mimetic comprises compound 42 or an isomer, tautomer, salt, solvate, or polymorph thereof.