The reactions of Ln(NO(3))(3) (Ln = La, Er) with 1,4-phenylendiacetic acid (H(2)PDA) under hydrothermal conditions produce isostructural lanthanide coordination polymers with the empirical formula [Ln(2)(PDA)(3)(H(2)O)] x 2H(2)O. The extended structure of [Ln(2)(PDA)(3)(H(2)O)] x 2H(2)O consists of Ln-COO triple helices cross-linked through the [bond]CH(2)C(6)H(4)CH(2)[bond] spacers of the PDA anions, showing 1D open channels along the crystallographic c axis that accommodate the guest and coordinated water molecules. Evacuation of [Er(2)(PDA)(3)(H(2)O)] x 2H(2)O at room temperature and at 200 degrees C, respectively, generates [Er(2)(PDA)(3)(H(2)O)] and [Er(2)(PDA)(3)], both of which give powder X-ray diffraction patterns consistent with that of [Er(2)(PDA)(3)(H(2)O)] x 2H(2)O. The porosity of [Er(2)(PDA)(3)(H(2)O)] and [Er(2)(PDA)(3)] is further demonstrated by their ability to adsorb water vapor to form [Er(2)(PDA)(3)(H(2)O)] x 2H(2)O quantitatively. Thermogravimetric analyses show that [Er(2)(PDA)(3)] remains stable up to 450 degrees C. The effective pore window size in [Er(2)(PDA)(3)] is estimated at 3.4 A. Gas adsorption measurements indicate that [Er(2)(PDA)(3)] adsorbs CO(2) into its pores and shows nonporous behavior toward Ar or N(2). There is a general correlation between the pore size and the kinetic diameters of the adsorbates (CO(2) = 3.3 A, Ar = 3.40 A, and N(2) = 3.64 A). That the adsorption favors CO(2) over Ar is unprecedented and may arise from the combined differentiations on size and on host-guest interactions.

Glycopeptides are extremely useful for basic research and clinical applications, but access to structurally-defined glycopeptides is limited by the difficulties in synthesizing this class of compounds. In this study, we demonstrate that many common peptide coupling conditions used to prepare O-linked glycopeptides result in substantial amounts of epimerization at the alpha position. In fact, epimerization resulted in up to 80% of the non-natural epimer, indicating that it can be the major product in some reactions. Through a series of mechanistic studies, we demonstrate that the enhanced epimerization relative to non-glycosylated amino acids is due to a combination of factors, including a faster rate of epimerization, an energetic preference for the unnatural epimer over the natural epimer, and a slower overall rate of peptide coupling. In addition, we demonstrate that use of 2,4,6-trimethylpyridine (TMP) as the base in peptide couplings produces glycopeptides with high efficiency and low epimerization. The information and improved reaction conditions will facilitate the preparation of glycopeptides as therapeutic compounds and vaccine antigens.

The antiproliferative factor (APF) involved in interstitial cystitis is a glycosylated nonapeptide (TVPAAVVVA) containing a sialylated core α-O-disaccharide linked to the N-terminal threonine. The chemical structure of APF was deduced using spectroscopic techniques and confirmed using total synthesis. The synthetic APF provided a platform to study amino acid modifications and their effect on APF activity, based on which a structure-activity relationship (SAR) for APF activity was previously proposed. However, this SAR model could not explain the change in activity associated with minor alterations in the peptide sequence. Presented is computational analysis of 14 APF derivatives to identify structural trends from which a more detailed SAR is obtained. The APF activity is found to be dictated by the close interplay between carbohydrate-peptide and peptide-peptide interactions. The former involves hydrogen bond and hydrophobic interactions and the latter is dominated by hydrophobic interactions. The highly flexible hydrophobic peptide adopts collapsed conformations separated by low energy barriers. APF activity correlates with hydrophobic clustering associated with amino acids 4A, 6V and 8V. Peptide conformations are highly sensitive to single point mutations, which explain the experimental trends. The presented SAR will act as a guide for lead optimization of more potent APF analogues of potential therapeutic utility.