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Diamidine molecules, which have been recognized as the powerful gene drug candidates over the past decades, can bind in the DNA minor groove, inhibit the duplication of morbid sequences, and fight against a number of human and animal diseases. In this paper, on the basis of the binding models of a series of diamidines with DNA, the important influencing factors for the binding affinity of diamidines with DNA were systematically analyzed. The obtained results demonstrated that the curvature, length, distal group, and heteroaromatic ring of diamidine are four important factors, which could influence their binding affinities. Specifically, the better the curvature of the diamidine fits DNA minor groove, the higher the binding affinity is; increasing the molecular length within a certain range can make the binding affinity higher; changing the distal group of diamidine from amidino to imidazole or pyrimidine is favorable for improving the corresponding binding affinity; and the introduction of central heteroaromatic rings of diamidine molecules influences their binding affinities. One diamidine (named as DB103d) with ideal DNA binding affinity validates the four important factors proposed in the present work. The results obtained in this work might be helpful for the design of new efficient diamidine-based drug candidates. [ABSTRACT FROM AUTHOR]

The inclusion complexes of two modified cyclic decapeptides with 1-phenyl-1-propanol ( PP) enantiomers were first studied using the density functional theory B3LYP method. Our calculated results indicated that modified cyclic decapeptide ( CM-CDP and DA-CDP) could form stable inclusion complexes. Significantly, based on the structural characteristics and hydrogen bond analyses, we found that the primary driving force of inclusion complex formation is a cooperative work of hydrogen bonds, steric effect, and electronic interactions, which facilitates the enhancement of binding affinity of the PP enantiomers with CM-CDP and DA-CDP. The current study shows that modified cyclic decapeptide is a desirable host molecule for chiral and molecular recognition. [ABSTRACT FROM AUTHOR]