Search results for: Darren A. Thompson

Items from 1 to 14 out of 14 results

article

Fast three‐dimensional phase retrieval in propagation‐based X‐ray tomography

Darren A. Thompson, Yakov I. Nesterets, Konstantin M. Pavlov, Timur E. Gureyev

Journal of Synchrotron Radiation > 26 > 3 > 825 - 838

The following article describes a method for 3D reconstruction of multi‐material objects based on propagation‐based X‐ray phase‐contrast tomography (PB‐CT) with phase retrieval using the homogeneous form of the transport of intensity equation (TIE‐Hom). Unlike conventional PB‐CT algorithms that perform phase retrieval of individual projections, the described post‐reconstruction phase‐retrieval method...

article

Arginine selective reagents for ligation to peptides and proteins

Darren A. Thompson, Raymond Ng, Philip E. Dawson

Journal of Peptide Science > 22 > 5 > 311 - 319

A new class of arginine‐specific bioconjugation reagents for protein labeling has been developed. This method utilizes a triazolyl‐phenylglyoxal group on the probe molecule that reacts selectively with the guandinyl group of Arg residues in a protein or peptide. The reaction proceeds in neutral to basic bicarbonate buffers and is selective for arginine residues in peptides and folded proteins. Importantly,...

article

Adapter reagents for protein site specific dye labeling

Darren A. Thompson, Eric G. B. Evans, Tomas Kasza, Glenn L. Millhauser, more

Biopolymers > 102 > 3 > 273 - 279

Chemoselective protein labeling remains a significant challenge in chemical biology. Although many selective labeling chemistries have been reported, the practicalities of matching the reaction with appropriately functionalized proteins and labeling reagents is often a challenge. For example, we encountered the challenge of site specifically labeling the cellular form of the murine Prion protein with...

article

A POMC variant implicates β-melanocyte-stimulating hormone in the control of human energy balance

Yung Seng Lee, Ben G. Challis, Darren A. Thompson, Giles S.H. Yeo, more

Cell Metabolism > 2006 > 3 > 2 > 135-140

The melanocortin-4 receptor (MC4R) plays a critical role in the control of energy balance. Of its two pro-opiomelanocortin (POMC)-derived ligands, α- and β-MSH, the majority of attention has focused on α-MSH, partly reflecting the absence of β-MSH in rodents. We screened the POMC gene in 538 patients with severe, early-onset obesity and identified five unrelated probands who were heterozygous for...

article

Chimeras of the agouti-related protein: Insights into agonist and antagonist selectivity of melanocortin receptors

Pilgrim J. Jackson, Bin Yu, Benjamin Hunrichs, Darren A. Thompson, more

Peptides > 2005 > 26 > 10 > 1978-1987

The specific melanocortin receptors, MC3R and MC4R, are directly linked to metabolism and body weight control. These receptors are activated by the peptide hormone α-MSH and antagonized by the agouti-related protein (AGRP). Whereas α-MSH acts broadly on most members of the MCR family (with the exception of MC2R), AGRP is highly specific for only MC3R and MC4R. AGRP is a complex ligand of approximately...

article

Structures of the Agouti Signaling Protein

Joseph C. McNulty, Pilgrim J. Jackson, Darren A. Thompson, Biaoxin Chai, more

Journal of Molecular Biology > 2005 > 346 > 4 > 1059-1070

Expression of the agouti signaling protein (ASIP) during hair growth produces the red/yellow pigment pheomelanin. ASIP, and its neuropeptide homolog the agouti-related protein (AgRP) involved in energy balance, are novel, paracrine signaling molecules that act as inverse agonists at distinct subsets of melanocortin receptors. Ubiquitous ASIP expression in mice gives rise to a pleiotropic phenotype...

article

Peptoid mimics of agouti related protein

Darren A. Thompson, Biao-Xin Chai, Hilary L. E. Rood, Michael A. Siani, more

Bioorganic & Medicinal Chemistry Letters > 2003 > 13 > 8 > 1409-1413

The Agouti Related Protein (AGRP) is an endogenous antagonist of melanocortin-3 and -4 receptors, each of which plays a key role in body weight homeostasis. We designed a peptoid trimer based on AGRP 111-113 in which a single chiral atom is used to partially restrain the backbone structure. Peptoid 5 displaced both radiolabeled Nle4-α-MSH (IC ₅ ₀ =3.1 μM) and AGRP (86-132) (IC ₅ ...

article

Inverse agonist activity of agouti and agouti-related protein

Biao-Xin Chai, Richard R. Neubig, Glenn L. Millhauser, Darren A. Thompson, more

Peptides > 2003 > 24 > 4 > 603-609

Agouti and agouti-related protein (AgRP) are endogenous antagonists of the melanocortin receptors (MCxR). Previous data showed that recombinant full-length agouti and a synthetic fragment of AgRP, AgRP (83-132), are inverse agonists at the MC1R and MC4R, respectively. This study demonstrates the smaller analogs AgRP (87-120) and ASIP [90-132 (L89Y)], and short peptides Yc[CRFFNAFC]Y and Qc[CRFFRSAC]S...

article

Dap-SL: a new site-directed nitroxide spin labeling approach for determining structure and motions in synthesized peptides and proteins

Joe C. McNulty, Darren A. Thompson, Michael R. Carrasco, Glenn L. Millhauser

FEBS Letters > 2002 > 529 > 2-3 > 243-248

A new approach for site-directed placement of nitroxide spin labels in chemically synthesized peptides and proteins is described. The scheme takes advantage of a novel diaminopropionic acid scaffold to independently control backbone and side chain elongation. The result is a spin-labeled side chain, referred to as Dap-SL, in which an amide bond forms a linker between the nitroxide and the peptide...

article

Design, Pharmacology, and NMR Structure of a Minimized Cystine Knot with Agouti-Related Protein Activity ^†

Pilgrim J. Jackson, Joseph C. McNulty, Ying-Kui Yang, Darren A. Thompson, more

Biochemistry > 2002 > 41 > 24 > 7565 - 7572

article

High-Resolution NMR Structure of the Chemically-Synthesized Melanocortin Receptor Binding Domain AGRP(87−132) of the Agouti-Related Protein ^† ^, ^‡

Joseph C. McNulty, Darren A. Thompson, Kimberly A. Bolin, Jill Wilken, more

Biochemistry > 2001 > 40 > 51 > 15520 - 15527

article

NMR structure of a minimized human agouti related protein prepared by total chemical synthesis

Kimberly A. Bolin, D. Joe Anderson, Julie A. Trulson, Darren A. Thompson, more

FEBS Letters > 1999 > 451 > 2 > 125-131

The structure of the chemically synthesized C-terminal region of the human agouti related protein (AGRP) was determined by 2D ¹ H NMR. Referred to as minimized agouti related protein, MARP is a 46 residue polypeptide containing 10 Cys residues involved in five disulfide bonds that retains the biological activity of full length AGRP. AGRP is a mammalian signaling molecule, involved in weight...

article

Total chemical synthesis and high-resolution crystal structure of the potent anti-HIV protein AOP-RANTES

Jill Wilken, David Hoover, Darren A Thompson, Paul N Barlow, more

Chemistry & Biology > 1999 > 6 > 1 > 43-51

Background: RANTES is a CC-type chemokine protein that acts as a chemoattractant for several kinds of leukocytes, playing an important pro-inflammatory role. Entry of human immunodeficiency virus-1 (HIV-1) into cells depends on the chemokine receptor CCR5. RANTES binds CCR5 and inhibits HIV-1 entry into peripheral blood cells. Interaction with chemokine receptors involves a distinct set of residues...

article

Accessibility of selenomethionine proteins by total chemical synthesis: structural studies of human herpesvirus-8 MIP-II

Weiping Shao, Elias Fernandez, Jill Wilken, Darren A. Thompson, more

FEBS Letters > 1998 > 441 > 1 > 77-82

The determination of high resolution three-dimensional structures by X-ray crystallography or nuclear magnetic resonance (NMR) is a time-consuming process. Here we describe an approach to circumvent the cloning and expression of a recombinant protein as well as screening for heavy atom derivatives. The selenomethionine-modified chemokine macrophage inflammatory protein-II (MIP-II) from human herpesvirus-8...

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