Synthesis of Carboxy-Labeled C14-N,N-Diethyl-m-Toluamide, an Insect Repellent2

Green, Nathan

doi:10.1093/jee/51.5.707

Cited by 40 publications

(56 citation statements)

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“…However, an essential requirement for a biotinylated ligand of an avidin transport vector conjugate is monobiotinylation. Higher degrees of biotinylation inevitably cause aggregation by avidin, which has four binding sites for biotin (23). Therefore, in the present studies, a VIP analogue (VIPa) suitable for monobiotinylation was developed.…”

Section: Introductionmentioning

confidence: 99%

Pharmacologic effects in vivo in brain by vector-mediated peptide drug delivery.

Bickel

Yoshikawa²,

Landaw³

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

143

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Pharmacologic effects in brain caused by systemic administration of neuropeptides are prevented by poor transport of the peptide through the brain vascular endothelium, which comprises the blood-brain barrier in vivo. In the present study, successful application of a chimeric peptide approach to enhance drug delivery through the bloodbrain barrier for the purpose of achieving a central nervous system pharmacologic effect is described. The chimeric peptide was formed by linkage of a potent vasoactive intestinal peptide (VIP) analogue, which had been monobiotinylated, to a drug transport vector. The vector consisted of a covalent conijugate of avidin and the OX26 monoclonal antibody to the transferrin receptor. Owing to the high concentration of transferrin receptors on brain capillary endothelia, OX26 targets brain and undergoes receptor-mediated transcytosis through the bloodbrain barrier. Systemic infusion of low doses (12 pug/kg) of the VIP chimeric peptide in rats resulted in an in vivo central nervous system pharmacologic effect: a 65% increase in cerebral blood flow. Biotinylated VIP analogue without the brain transport vector was ineffective.Morphological, biochemical, and functional evidence indicates that vasoactive intestinal polypeptide (VIP) is a potent cerebrovascular vasodilator (1-6). Although VIP causes vasodilation in vitro (7, 8) and when applied locally to intracranial blood vessels (9), no consistent cerebrovascular effects could be demonstrated after systemic application of the peptide (10-12). This exemplifies the prohibitive role played by the blood-brain barrier (BBB) in limiting peptide transport to brain and subsequent neuropharmacologic effects. The use of chimeric peptides offers an approach to enhanced brain delivery of such peptides: drugs that normally do not cross the BBB may be coupled to brain drug transport vectors (13).Brain drug transport vectors include proteins such as cationized albumin (14) or the OX26 monoclonal antibody (15), which undergo absorptive-or receptor-mediated transcytosis through the BBB, respectively. OX26 is a murine monoclonal antibody directed against the rat transferrmn receptor (16). The transferrin receptor is highly expressed on brain capillary endothelium (16, 17) and allows for receptormediated transcytosis of circulating transferrin (18) or the OX26 monoclonal antibody (15,19) through the BBB.Coupling of drugs to brain transport vectors such as OX26 is facilitated by use of the avidin-biotin system (20), and cbupling of avidin to the transport vectors enables their potential application to delivery of biotinylated peptides or antisense oligonucleotides (21,22). However, an essential requirement for a biotinylated ligand of an avidin transport vector conjugate is monobiotinylation. Higher degrees of biotinylation inevitably cause aggregation by avidin, which has four binding sites for biotin (23). Therefore, in the present studies, a VIP analogue (VIPa) suitable for monobiotinylation was developed. To demonstrate an in vivo pharmacologic eff...

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Section: Introductionmentioning

confidence: 99%

Pharmacologic effects in vivo in brain by vector-mediated peptide drug delivery.

Bickel

Yoshikawa²,

Landaw³

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

143

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“…Owing to the remarkably high stability and high affinity of streptavidin for its natural ligand biotin (K d ϳ10 Ϫ15 M) (1), together with widespread bioanalytical, diagnostic, and therapeutic applications (2)(3)(4)(5), this protein has been extensively used to develop and validate such screening methodologies. High affinity unnatural ligands have been discovered by screening linear (6 -11) and cyclic (6) peptide libraries.…”

mentioning

confidence: 99%

In Crystals of Complexes of Streptavidin with Peptide Ligands Containing the HPQ Sequence the pK of the Peptide Histidine Is Less than 3.0

Katz

Cass

1997

Journal of Biological Chemistry

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Screening of peptide libraries either displayed on phage by molecular biology or produced by combinatorial chemical synthesis is an effective method for discovery of peptide ligands for diverse protein targets. Owing to the remarkably high stability and high affinity of streptavidin for its natural ligand biotin (K d ϳ10 Ϫ15 M) (1), together with widespread bioanalytical, diagnostic, and therapeutic applications (2-5), this protein has been extensively used to develop and validate such screening methodologies. High affinity unnatural ligands have been discovered by screening linear (6 -11) and cyclic (6) peptide libraries. Streptavidin also provides an ideal paradigm for probing the structural basis of high affinity protein-ligand interactions (12-16) and for introducing or improving properties by protein engineering (2, 17, 18). Finally, the high resolution crystal structures of apostreptavidin and of streptavidin-ligand complexes provide a powerful basis for developing structure-based ligand design strategies (12, 19 -23).Recently we described the structures of streptavidin-bound linear and cyclic peptide ligands containing the HPQ sequence (13) discovered by phage display and probed the structural basis for the higher affinities of the cyclic ligands compared with the corresponding linear ones. These structures enabled the successful design of cyclic peptide ligands conformationally constrained with designed thioether cross-links (22), of streptavidin dimerizing peptide ligands (19 -21), and of a streptavidinbinding small molecule ligand (12).The binding to streptavidin and avidin of certain small molecule and peptide ligands is pH-dependent. The affinities for avidin of biotin derivatives, 2-iminobiotin and diaminobiotin, decrease dramatically as the pH is lowered (24), as does the affinity for streptavidin of a linear peptide discovered by phage display, FSHPQNT (25). The extent of topochemical catalysis of disulfide formation and the resulting dimerization of designed streptavidin-bound HPQ-containing ligands whose thiols are presented next to one another in the crystal lattice also depend on pH (20).Determination of the pH dependence of ligand binding or of changes in properties incurred by ligand binding often yields insight into the mode of action (26 -28) or mechanism of binding (29 -36) in biological and chemical processes. Appraisal of the ionization states of groups in a protein-bound ligand or at the ligand binding site of the protein target may reveal some of the determinants of high affinity binding crucial for structurebased ligand design. To this end we determine the pH dependences of binding to streptavidin of linear and cyclic peptide ligands containing the HPQ sequence and probe the structural basis for the dependences through crystallographic determination of complexes at multiple pH values. The affinities for streptavidin at pH 3. 0, 4.0, 5.0, 6.0, 6.2, 6.4, 7.0, 7.3, 8.0, and 9.3 of linear Ac-AEFSHPQNTIEGRK-NH 2 , cyclo-Ac-AE[CH-PQGPPC]IEGRK-NH 2 , cyclo-Ac-AE[CHPQFC]IEGRK-NH 2 , and cyc...

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“…10 15 M −1 ) to biotin than that of SAv (Ka ca. 10 13 M −1 ) [168]. Although avidin has four possible reaction sites with biotin [169], the best experimental result shows a ratio of 1 (avidin): 2.89 (biotin) in an extremely high biotin concentration [167].…”

Section: Fig 18 Afm Images Of Only Sav-biotin ((A) and (B)) And Savmentioning

confidence: 99%

The principles and applications of nano-diagnosis system for a nano-biosensor

Kim

Chang

Muramatsu

et al. 2011

Korean J. Chem. Eng.

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In this review, the basic principles and research trends of biosensors are briefly described and a nano-sensing system applying QCM (quartz crystal micro-balance), nano-diagnosis methods by AFM (atomic force microscopy) and SNOAM (scanning near-field/atomic force microscopy) is discussed intensively. The principle, construction, and applications of piezoelectric crystal sensors as a universal sensor are reviewed. This review is focused mainly on liquid phase applications, such as immune-sensors, gelation detecting sensors, and cultured cell monitoring sensors. The principle of nano-diagnosis based on the AFM or SNOAM techniques is described in detail. Finally, the binding affinity of peptide probes to proteins using AFM and the visualizing of a hybridized PNA probe on a DNA molecule using SNOAM are evaluated and discussed.

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Synthesis of Carboxy-Labeled C14-N,N-Diethyl-m-Toluamide, an Insect Repellent2

Cited by 40 publications

References 0 publications

Pharmacologic effects in vivo in brain by vector-mediated peptide drug delivery.

Pharmacologic effects in vivo in brain by vector-mediated peptide drug delivery.

In Crystals of Complexes of Streptavidin with Peptide Ligands Containing the HPQ Sequence the pK of the Peptide Histidine Is Less than 3.0

The principles and applications of nano-diagnosis system for a nano-biosensor

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