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Recent Progress in Polymer Therapeutics as Nanomedicines
Published in Dan Peer, Handbook of Harnessing Biomaterials in Nanomedicine, 2021
Sahar Israeli Dangoor, Shani Koshrovski Michael, Hemda Baabur-Cohen, Liora Omer, Ronit Satchi-Fainaro
Recently, a novel class of polymer backbone in which the drug and the polymer backbone are connected via a non-covalent, biologically inspired binding motif, was proposed [68]. This linker consists of a pair of complementary peptides that are wound around each other in a super-helical fashion to form a tertiary structural motif that is referred to as coiled coil. In order to form the non-covalent polymer therapeutics, the polymeric carrier functionalized with one peptide is mixed in an aqueous solution with the drug of interest or targeting moiety, which is functionalized with the complementary sequence to the peptide. The drug will be intracellularly released once the conjugate is exposed to the relatively low pH of the endosomal compartment. Targeting moieties, such as recombinant single-chain antibody fragment (scFv) were also attached, noncovalently, to a polymer carrier via a coiled coil interaction. This combination demonstrated superior therapeutic efficiency compared the nontargeted polymer–drug conjugate in vivo [69]. These innovative coiled coil-based peptide linkers may be useful to form different compound libraries, depending on the pool of carriers and drugs that we create.
Genetically Engineered Protein Domains as Hydrogel Crosslinks
Published in Raphael M. Ottenbrite, Sung Wan Kim, Polymeric Drugs & Drug Delivery Systems, 2019
Chun Wang, Russell J. Stewart, Russell J. Stewart, Jindrich KopeČek
One common folding motif of proteins is the coiled coil, which is a slightly left-handed super-helix consisting of two or more right-handed a-helices [21]. The coiled-coil motif has been found in over 200 native proteins, and this number is growing rapidly. The primary structure of the coiled-coil strands has the characteristic 4–3 (heptad) repeats. One heptad constitutes exactly two turns, each covering three and a half residues. As illustrated in Figure 1, amino acid residues in a heptad are designated as “a, b, c, d, e, f, g.” Hydrophobic residues at “a” and “d” positions pack their side chains tightly in aqueous environment and form the stabilizing interfaces between the helices. Other residues are usually polar ones. In particular, ionic interactions between “e” and “g” residues are important in specific association among helices.
Structures
Published in Thomas M. Nordlund, Peter M. Hoffmann, Quantitative Understanding of Biosystems, 2019
Thomas M. Nordlund, Peter M. Hoffmann
One of the reasons keratin crystals do not readily form is an interaction we have discussed in general but not applied specifically to keratin. The lowest-level structure of an α keratin consists of α-helical domains that consist of amino acid repeats of a pattern of seven, ABCDEFG. A and D are hydrophobic amino acids. This “heptad” repeat is characteristic of sequences able to form coiled-coil structures.15 What structural consequences do these heptads have? One basic feature of the α helix is that there are about 3.6 residues per turn. This means that every fourth amino acid will be on the same side of the helix as the first but offset a bit. This offset will create a hydrophobic line that will wind around the outside of the helix. When two such α helices come near each other, the hydrophobic interaction will tend to make the two helices wind around each other—a helix of helices.
A coarse-grained model of the effective interaction for charged amino acid residues and its application to formation of GCN4-pLI tetramer
Published in Molecular Physics, 2018
Kazutomo Kawaguchi, Satoshi Nakagawa, Isman Kurniawan, Koichi Kodama, Muhammad Saleh Arwansyah, Hidemi Nagao
GCN4-pLI is one of the GCN4 leucine zipper mutants and a coiled-coil composed of four α-helices wrapped around each other to bury a hydrophobic core [1]. The formation of GCN4-pLI tetramer is dominated by both hydrophobic and electrostatic interaction between monomers. While the association of the tetramer is dominated by hydrophobic interaction, the helix orientation is dominated by the salt bridge arising from the electrostatic interaction between charged amino acid residues [2]. In their experiment, only all-parallel helices have been observed after 36 h because of the salt bridge between charged amino acid residues, although anti-parallel four-helix bundle conformations have been prepared in solution.
Self-organisation of rhombitruncated cuboctahedral hexagonal columns from an amphiphilic Janus dendrimer
Published in Molecular Physics, 2021
Ning Huang, Qi Xiao, Mihai Peterca, Xiangbing Zeng, Virgil Percec
There are three possible directions equivalent to [421] at the corner of the unit cell (yellow spheres) (Figure 10a upper). In addition, there are other three possible directions which are different but also equivalent to [421] that start from the body centre of the Pmn unit cell (yellow sphere) (Figure 10a lower). Due to the symmetry of the cubic lattice, the number of directions equivalent to [421] is 8 times the 6 directions mentioned in Figure 9a, which represents 48 directions in total (Figure 10b, c). Figure 10b illustrates the 48 directions that hexagonal arrays of columns form via the SOM effect. These directions are generated with hexagonal arrays of columns as shown in Figure 10c. This arrangement corresponds to a rhombitruncated cuboctahedron, that to the best of our knowledge, although more primitive than biological assemblies created from proteins, was never encountered in biology or in synthetic supramolecular chemistry. Bundles of α-helical proteins are widely available in biology. They were discovered simultaneously and independently by Pauling and Corey [110] and by Crick [111] and are known as coiled-coil α-helix protein structures. Recently, a periodic table of coiled-coil proteins was elaborated [112]. Mimics of three and four-bundles of helical columns were elaborated by our laboratory via complex multistep synthetic methods [16,17,113–116]. However, the simplicity of the SOM method for the design of bundles of helical columns organised in unprecedentedly complex architectures such as tetrahedral [63], orthogonal [62], distorted dodecahedral [65] and now in rhombitruncated cuboctahedral arrangement of hexagonal columns as shown in the present report (Figure 11) seems to exceed even the ability of biology, although with a much lower level of perfection. We would like to stress again that in view of the results reported here, the distorted dodecahedral morphology [65] will have to be reinvestigated. This will be done and reported in a different publication. Elucidating the mechanism of the SOM concept and extending it to other F-K phases will provide access, most probably, to even more complex architectures.