The influence of molecular conformation upon the self-assembly of cyclohexane diamide diacids.
BACKGROUND
Information regarding the self-association of small peptide motifs can be used in the design of peptide microstructures. Previous work in our laboratories illustrated the self-association of certain diamide diacids into microcapsules. In this report a series of cyclohexane diamide diacids are investigated. The cyclohexylene (R-C6H10-R) system (with its axial and equatorial requirements) provided an opportunity to study the influence of molecular conformation upon the self-aggregation process.


RESULTS
Condensation of the respective cis- and trans-1,2-, 1,3-, and 1,4- cyclohexane dicarboxylic acid platforms with two equivalents of a L-Phe ester followed by deprotection gave the desired diamide diacids. Basic solutions of cis-1,2-, trans-1,3-, and cis-1,4-diamide diacids generated solid microspheres when acidified to pH 2.4. Molecular modeling revealed that 1,3-diaxial interactions favor a helical turn within these diamides.


CONCLUSIONS
Access to 'complementary' molecular geometries is needed to self-associate into microscopic architectures.
Bergeron
R J
RJ
Department of Medicinal Chemistry, University of Florida, J. Hillis Miller Health Center, Gainesville 32610, USA.
Yao
G W
GW
Erdos
G W
GW
Milstein
S
S
Gao
F
F
Rocca
J
J
Weimar
W R
WR
Price
H L
HL
Phanstiel
O
O
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry*; D002214:Capsules / Q000138:chemical synthesis; D003510:Cyclohexanes / Q000737:chemistry*; D003998:Dicarboxylic Acids / Q000737:chemistry*; D015195:Drug Design; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D008958:Models, Molecular; D011487:Protein Conformation; D017550:Spectroscopy, Fourier Transform Infrared
D000577:Amides; D002214:Capsules; D003510:Cyclohexanes; D003998:Dicarboxylic Acids