Novel peptide antagonists of adrenomedullin and calcitonin gene-related peptide receptors:identification, pharmacological characterization, and interactions with position 74 in receptor activity-modifying protein 1/3

Human adrenomedullin (AM) is a 52-amino acid peptide belonging to the calcitonin peptide family, which also includes calcitonin gene-related peptide (CGRP) and AM2. The two AM receptors, AM(1) and AM(2), are calcitonin receptor-like receptor (CL)/receptor activity-modifying protein (RAMP) (RAMP2 and RAMP3, respectively) heterodimers. CGRP receptors comprise CL/RAMP1. The only human AM receptor antagonist (AM(22-52)) is a truncated form of AM; it has low affinity and is only weakly selective for AM(1) over AM(2) receptors. To develop novel AM receptor antagonists, we explored the importance of different regions of AM in interactions with AM(1), AM(2), and CGRP receptors. AM(22-52) was the framework for generating further AM fragments (AM(26-52) and AM(30-52)), novel AM/alphaCGRP chimeras (C1-C5 and C9), and AM/AM(2) chimeras (C6-C8). cAMP assays were used to screen the antagonists at all receptors to determine their affinity and selectivity. Circular dichroism spectroscopy was used to investigate the secondary structures of AM and its related peptides. The data indicate that the structures of AM, AM2, and alphaCGRP differ from one another. Our chimeric approach enabled the identification of two nonselective high-affinity antagonists of AM(1), AM(2), and CGRP receptors (C2 and C6), one high-affinity antagonist of AM(2) receptors (C7), and a weak antagonist selective for the CGRP receptor (C5). By use of receptor mutagenesis, we also determined that the C-terminal nine amino acids of AM seem to be responsible for its interaction with Glu74 of RAMP3. We provide new information on the structure-activity relationship of AM, alphaCGRP, and AM2 and how AM interacts with CGRP and AM(2) receptors.

Polarization-independent high-resolution spectral interrogation of FBGs using a BFBG-CCD array for optical sensing applications

Optical fibre strain sensors using Fibre Bragg Gratings (FBGs) are poised to play a major role in structural health monitoring in a variety of application from aerospace to civil engineering. At the heart of technology is the optoelectronic instrumentation required to convert optical signals into measurands. Users are demanding compact, lightweight, rugged and low cost solutions. This paper describes development of a new device based on a blazed FBG and CCD array that can potentially meet the above demands. We have shown that this very low cost technique may be used to interrogate a WDM array of sensor gratings with highly accurate and highly repeatable results unaffected by the polarisation state of the radiation. In this paper, we present results showing that sensors may be interrogated with an RMS error of 1.7pm, drift below 0.12pm and dynamic range of up to 65nm.

Polarization-independent high-resolution spectral interrogation of FBGs using a BFBG-CCD array for optical sensing applications

Optical fibre strain sensors using Fibre Bragg Gratings (FBGs) are poised to play a major role in structural health monitoring in a variety of application from aerospace to civil engineering. At the heart of technology is the optoelectronic instrumentation required to convert optical signals into measurands. Users are demanding compact, lightweight, rugged and low cost solutions. This paper describes development of a new device based on a blazed FBG and CCD array that can potentially meet the above demands. We have shown that this very low cost technique may be used to interrogate a WDM array of sensor gratings with highly accurate and highly repeatable results unaffected by the polarisation state of the radiation. In this paper, we present results showing that sensors may be interrogated with an RMS error of 1.7pm, drift below 0.12pm and dynamic range of up to 65nm.