High Temperature SELMA: Evolution of DNA-Supported Oligomannose Clusters Which Are Tightly Recognized by HIV bnAb 2G12

SELMA (SELection with Modified Aptamers) is a directed evolution method which can be used to develop DNA-supported clusters of carbohydrates in which the geometry of clustering is optimized for strong recognition by a lectin of interest. Herein, we report a modification of SELMA which results in glycoclusters which achieve dramatically stronger target recognition (100-fold) with dramatically fewer glycans (2–3-fold). Our first applications of SELMA yielded clusters of 5–10 oligomannose glycans which were recognized by broadly neutralizing HIV antibody 2G12 with moderate affinities (150–500 nM <i>K</i>_d’s). In the present manuscript, we report glycoclusters containing just 3–4 glycans, which are recognized by 2G12 with <i>K</i>_d’s as low as 1.7 nM. <i>These glycoclusters are recognized by 2G12 as tightly as is the HIV envelope protein gp120, and they are the first constructs to achieve this tight recognition with the minimal number of Man</i>_<i>9</i> <i>units (3–4) necessary to occupy the binding sites on 2G12.</i> They are thus of great interest as immunogens which might elicit broadly neutralizing antibodies against HIV

Directed Evolution of Multivalent Glycopeptides Tightly Recognized by HIV Antibody 2G12

Herein, we report a method for in vitro selection of multivalent glycopeptides, combining mRNA display with incorporation of unnatural amino acids and “click” chemistry. We have demonstrated the use of this method to design potential glycopeptide vaccines against HIV. From libraries of ∼10¹³ glycopeptides containing multiple Man₉ glycan(s), we selected variants that bind to HIV broadly neutralizing antibody 2G12 with picomolar to low nanomolar affinity. This is comparable to the strength of the natural 2G12–gp120 interaction, and is the strongest affinity achieved to date with constructs containing 3–5 glycans. These glycopeptides are therefore of great interest in HIV vaccine design

Zirconium Metal–Organic Frameworks Assembled from Pd and Pt P^NN^NP Pincer Complexes: Synthesis, Postsynthetic Modification, and Lewis Acid Catalysis

Carboxylic acid-functionalized Pd and Pt P^NN^NP pincer complexes were used for the assembly of two porous Zr metal–organic frameworks (MOFs), 2-PdX and 2-PtX. Powder X-ray diffraction analysis shows that the new MOFs adopt cubic framework structures similar to the previously reported Zr₆O₄(OH)₄[(P^OC^OP)­PdX]₃, [P^OC^OP = 2,6-(OPAr₂)₂C₆H₃); Ar = <i>p</i>-C₆H₄CO₂^–, X = Cl^–, I^–] (1-PdX). Elemental analysis and spectroscopic characterization indicate the presence of missing linker defects, and 2-PdX and 2-PtX were formulated as Zr₆O₄(OH)₄(OAc)_2.4[M­(P^NN^NP)­X]_2.4 [M = Pd, Pt; P^NN^NP = 2,6-(HNPAr₂)₂C₅H₃N; Ar = <i>p</i>-C₆H₄CO₂^–; X = Cl^–, I^–]. Postsynthetic halide ligand exchange reactions were carried out by treating 2-PdX with Ag­(O₃SCF₃) or NaI followed by PhI­(O₂CCF₃)₂. The latter strategy proved to be more effective at activating the MOF for the catalytic intramolecular hydroamination of an <i>o</i>-substituted alkynyl aniline, underscoring the advantage of using halide exchange reagents that produce soluble byproducts