Linker molecules

Fig. 4. Typical AFM rupture experiment (top) Receptor molecules are fixed via linker molecules to a surface (left) in the same way, ligand molecules are connected to the AFM cantilever (right). When pulling the cantilever towards the right, the pulling force applied to the ligand can be measured. At the point of rupture of t he ligand-receptor complex the measured force abruptly drops to zero so that the rupture force can be measured.

To enable an atomic interpretation of the AFM experiments, we have developed a molecular dynamics technique to simulate these experiments [49], Prom such force simulations rupture models at atomic resolution were derived and checked by comparisons of the computed rupture forces with the experimental ones. In order to facilitate such checks, the simulations have been set up to resemble the AFM experiment in as many details as possible (Fig. 4, bottom) the protein-ligand complex was simulated in atomic detail starting from the crystal structure, water solvent was included within the simulation system to account for solvation effects, the protein was held in place by keeping its center of mass fixed (so that internal motions were not hindered), the cantilever was simulated by use of a harmonic spring potential and, finally, the simulated cantilever was connected to the particular atom of the ligand, to which in the AFM experiment the linker molecule was connected. 

Fig. 8. De novo designed a-hehcal proteins. Dimers of the amphiphilic helix-forming peptide a B, GELEELLKKLKELLKG (see Table 1), in which the nature of the linker connecting the individual heflces plays a critical role in the stmcture of the final protein, (a) Using a Pro residue as the linker, ie, a B-Pro-a B, three molecules aggregated to form a trimeric coded-cod. (b) Using Pro-Arg-Arg as the linker, ie, a B-Pro-Aig-Arg-a, resulted in the...

There is a large range of resins available for SPOS. These resins are derivatised polymer supports with a range of linkers. The roles of linkers are (i) to provide point(s) of attachment for the tethered molecule, akin to a solid supported protecting group(s), (ii) to provide distance from the polymeric backbone in order to minimise interactions with the backbone, (iii) to enable cleavage of product molecules under conditions compatible with the stability of the molecules and the reaction conditions employed for chemical transformations. Hence in order to... 

Figure 6.21 Schematic diagram of the conformational changes of calmodulin upon peptide binding, (a) In the free form the calmodulin molecule is dumhhell-shaped comprising two domains (red and green), each having two EF hands with bound calcium (yellow), (b) In the form with bound peptides (blue) the a helix linker has been broken, the two ends of the molecule are close together and they form a compact globular complex. The internal structure of each domain is essentially unchanged. The hound peptide binds as an a helix.

Figure 13.31 Space-filling diagram of Src tyrosine kinase in the same view as Figure 13.30. The SH2 domain makes only a few contacts with the rest of the molecule except for the tail region of the kinase. The SH3 domain contacts the N-domain of the kinase in addition to the linker region. There are extensive contacts between the N- and C-domains of the kinase. (Adapted from W. Xu et al., Nature 385 596-602, 1997.)...

Pulici and coworkers have reported a solid-phase variation of the Robinson-Gabriel for the production of parallel libraries of ox azole-containing molecules." The preparation is based on a solid supported 2-acylamino ketone 16 that can be cleaved by means of a volatile anhydride and cyclized in solution to obtain a substituted oxazole ring (17) that does not contain traces of the linker moiety. 

Fibronectin receptor is a two-chain glycoprotein of the integrin family that serves as a transmembrane linker by binding to talin on the cytoplasmic side and to fibronectin on the external side of the membrane. The pull exerted by stress fibers on attached structures may be produced by bipolar assemblies of nonmuscle myosin molecules producing a sliding of actin filaments of opposite polarity. 

This effect is particularly well documented for y - and -amino acid residues [217, 218] which in several natural products (bleomycin A2 [219], calyculins [220]) have been shown to play a substantial role in the pre-organization of the whole molecule into its bioactive conformation. For example, changes in the substitution pattern of the y-amino acid linker in bleomycin A2 result in reduced DNA cleavage efficiency [219]. In the case of y-peptides, changing the relative configuration like or unlike of y " -amino acids has been used as a strategy to generate different local conformations (Fig. 2.34) suitable either for the construction of helices [201] or turns ]202-204]. 

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