Fibrillins are the major glycoprotein components of microfibrils that form a template for tropoelastin during elastic fibrillogenesis. We have examined cell adhesion to assembled purified microfibrils, and its molecular basis. Human dermal fibroblasts exhibited Arg-Gly-Asp and cation-dependent adhesion to microfibrils and recombinant fibrillin-1 protein fragments. Strong integrin ␣ 5 ␤ 1 interactions with fibrillin ligands were identified, but integrin ␣ v ␤ 3 also contributed to cell adhesion. Fluorescence-activated cell sorting analysis confirmed the presence of abundant ␣ 5 ␤ 1 and some ␣ v ␤ 3 receptors on these cells. Adhesion to microfibrils and to Arg-Gly-Aspcontaining fibrillin-1 protein fragments induced signaling events that led to cell spreading, altered cytoskeletal organization, and enhanced extracellular fibrillin-1 deposition. Differences in cell shape when plated on fibrillin or fibronectin implied substrate-specific ␣ 5 ␤ 1 -mediated cellular responses. An Arg-Gly-Asp-independent cell adhesion sequence was also identified within fibrillin-1. Adhesion and spreading of smooth muscle cells on fibrillin ligands was enhanced by antibody-induced ␤ 1 integrin activation. A375-SM melanoma cells bound Arg-Gly-Asp-containing fibrillin-1 protein fragments mainly through ␣ v ␤ 3 , whereas HT1080 cells used mainly ␣ 5 ␤ 1 . This study has shown that fibrillin microfibrils mediate cell adhesion, that ␣ 5 ␤ 1 and ␣ v ␤ 3 are both important but cell-specific fibrillin-1 receptors, and that cellular interactions with fibrillin-1 influence cell behavior.Fibrillins are large cysteine-rich glycoproteins and the major constituents of fibrillin-rich microfibrils of the extracellular matrix (ECM) 1 (1, 2). They are multidomain molecules, containing 47 epidermal growth factor (EGF)-like domains and 8-cysteine (TB) modules. Fibrillin-1 and fibrillin-2 are both expressed during fetal development, but fibrillin-1 isoform is by far the most abundant isoform in adult tissues (3, 4). The possibility that fibrillins interact with cell receptors was suggested by electron microscopy of vascular and other tissues showing juxtaposition of extracellular microfibrils and cellular dense plaques (5) and by the discovery that fibrillins contain the Arg-Gly-Asp (RGD) putative cell attachment motif (6). Integrins are ␣␤ heterodimeric transmembrane receptors that mediate cell adhesion to the ECM, usually through the characteristic RGD motif, and have widespread essential functions in development, tissue organization, and the immune system (7). Integrin-mediated cell interactions regulate cell adhesion and migration and initiate signaling pathways that lead to reorganization of actin cytoskeleton and cellular proliferative and secretory responses.Fibrillin-1 contains one RGD sequence in the fourth TB module (6). Fibrillin-2 contains two RGD sequences, one in the same position as the fibrillin-1 RGD sequence in the fourth TB module and the other in the third TB module where it is surrounded by hydrophobic amino acids (8). Fibrillin-3 also ...

In the Rh 2 (OAc) 4 -catalyzed amidoglycosylation of glucal 3-carbamates, anomeric stereoselectivity and the extent of competing C3-H oxidation depend on the 4O and 6O protecting groups. Acyclic protection permits high α-anomer selectivity with further improvement in less polar solvents, while electron-withdrawing protecting groups limit C3-oxidized byproducts. Stereocontrol and bifurcation between alkene insertion and C3-H oxidation reflect an interplay of conformational, stereoelectronic, and inductive factors.2-Amino sugars having a 2,3-cis stereo array include N-acetylmannosamine (ManNAc, 1), which is the biosynthetic precursor of the sialic acids, 1 and 2-allosamine, a constituent of the potent chitinase inhibitor allosamidin (2) 2 and a useful ligand scaffold (3) 3 for asymmetric catalysis. The challenge of stereoselective C2-N bond construction is acute in these systems, and control of anomeric configuration in the preparation of glycoside derivatives is desirable. Synthetic methods based on intermolecular additions to glycals typically place the C2-N group trans to the C3-oxygen substituent. 4 Gin's activated-sulfoxide-mediated acetamidoglycosylation 5 of glucals is an exception, producing ManNAc structures, though with N-acetylglucosamine (GlcNAc) byproducts. 5cAs an alternative, 6 we have used intramolecular nitrogen atom delivery from allal 3-azidoformates, 7 allal 3-carbamates, 8 and glucal 3-carbamates 9 to establish the 2,3-cis relationship. With the 3O-carbamoyl glycals, we extended Du Bois's C-H amidation method 10 to alkene insertion, 11,12 a new reaction of allylic carbamates. 13 Mechanistic studies 14 imply that these conditions produce rhodium nitrenoids having reactivity strikingly analogous to metal carbenoids. 15 With iodosobenzene (PhIO) 16 instead of PhI(OAc) 2 as the oxidant, we achieved in situ glycosylation of alcohols without nucleophilic competition from acetate, an overall amidoglycosylation process. 8,9,17 Allal frameworks (e.g., 4, Scheme 1) provided high 1,2-trans selectivity, offering a concise route to β-linked 2-amido allopyranosides as found in allosamidin. 7,8 However, in the C3-epimeric series, our one-pot amidoglycosylation process applied to glucal 3-carbamates 6a and 6b, having 4O,6O acetonide or di-tert-butylsilylene protection, gave anomeric mixtures only slighly favoring the 1,2-trans products 7-α and also generated dihydropyranone byproducts 8a and 8b via oxidation at the C3-H bond (Table 1, entries 1 and 5). 9 Using 4-penten-1-ol as the acceptor, we were able to stereoconvergently advance either anomer of n-pentenyl glycoside 18 7a, but the lack of amidoglycosylation selectivity stymied direct access to α-linked ManNAc derivatives. 9Herein we report that proper choice of 4O and 6O protecting groups and solvent enables high levels of stereocontrol and chemoselectivity in amidoglycosylation of glucal 3-carbamates. Our studies also illuminate electronic and conformational aspects of both amidoglycosylation and the competing C3-H oxidation.For comparison, we be...

The development of a remote, synchronous general chemistry lab course, which was offered to 800 students in the fall semester of 2020, is described. The course was designed with similar curricular goals as our in-person lab course and featured chemistry kits developed by a team of faculty, staff, and graduate TAs. The kits, which were distributed via a rental program through the university bookstore, provided students the opportunity to conduct hands-on experiments at home or in their dorm room. To create the remote lab course, the team negotiated logistical and curricular issues such as finding alternatives to costly precision glassware and instrumentation, adding strategies for engaging students online, decreasing chemical hazards of experiments, and encouraging a safety culture for students working remotely. A professional development graduate course for TA instructors, associated with the general chemistry lab program, was also enhanced by including topics that were relevant for understanding remote learning environments. In redesigning the lab course for remote delivery, we developed new experiments (e.g., calibration), introduced new engagement strategies (e.g., badging), revised several experiments (e.g., heats of reaction), included an Arduinobased spectrometer (e.g., visible spectroscopy and pulse oximetry), and provided new student supports (e.g., TAs on-call). Survey data was gathered to assess student evaluation of the hands-on activities, the presence of synchronous TA help, the badging experience, the value of the lab course, and challenges faced in taking the lab course during a pandemic.