Synthesis, Structure and Neurotoxicity of the Ab
Peptide of Alzheimer's Disease. Pp. 271-280.
Colin J. Barrow
[Abstract]
Influence of Centrally-Administered Peptides on Thirst and Sodium Appetite.
Pp. 281-294.
Richard S. Weisinger and Peta Burns
[Abstract]
Anticariogenic Casein Phosphopeptides. Pp. 295-304.
Eric C. Reynolds
[Abstract]
New Aspects of Angiotensin Receptor Regulation: Implications for Other
Seven Transmembrane-Spanning Receptors. Pp. 305-318.
Walter G. Thomas
[Abstract]
Recent Applications of Instrumental Biosensors for Protein and Peptide
Structure-Function Studies. Pp. 319-340.
Bruno Catimel, Teresa Domagala, Maureen Nerrie, Janet Weinstock,
Sara White, Helen Abud, Joan Heath and Edouard Nice
[Abstract]
Applications of NMR in Drug Design: Structure-Activity Relationships
in Disulfide-Rich Peptides. Pp. 341-350.
David J. Craik
[Abstract]
[Back to top] Synthesis,
Structure and Neurotoxicity of the Ab Peptide
of Alzheimer's Disease. Colin J. Barrow.
Amyloid formation and the Ab peptide are
central to the neuropathology of Alzheimer's disease. This review discusses
our work and related studies aimed at understanding the relationship between
structure and neurotoxicity for the Ab peptide.
These studies provide information on the importance of endogenous structural
variants, metal coordination, conformation, and aggregation state, to the
amyloidogenicity and neurotoxicity of the Ab
peptide. Also discussed is improved methodology for the synthesis of this
difficult peptide.
[Back to top] Influence
of Centrally-Administered Peptides on Thirst and Sodium Appetite. Richard
S. Weisinger and Peta Burns.
This review outlines current knowledge regarding the actions of centrally-administered
peptides on the intake of water and/or sodium solutions as well as the
possible mechanisms involved. Some peptides facilitate (e.g., angiotensin
II), while others decrease or inhibit intake (e.g., somatostatin). Identification
of these peptides and/or their receptors in brain regions involved in body
fluid and sodium homeostasis, such as the subfornical organ and organum
vasculosum of the lamina terminalis, suggests their physiological importance.
[Back to top] Anticariogenic
Casein Phosphopeptides. Eric C. Reynolds.
Proteins and peptides containing clusters of phosphoseryl residues
have been shown to stabilize amorphous calcium phosphate in solution, and
have been implicated in the regulation of biomineralisation processes.
Casein phosphopeptides (CPP) containing the cluster sequence -Ser(P)-Ser(P)-Ser(P)-Glu-Glu-
have been demonstrated to significantly reduce the level of dental caries
(tooth decay) in animal and human experiments and also to repair early
stages of decay. Through their multiple phosphoseryl residues the peptides
bind to forming nanoclusters of amorphous calcium phosphate (ACP) in metastable
solution, preventing their growth to the critical size required for nucleation
and phase transformation. Conformational and binding studies have shown
that all the phosphoseryl residues are important in interaction with ACP.
The CPP localise ACP at the tooth surface providing a reservoir of calcium
and phosphate ions thereby helping to maintain a state of supersaturation
with respect to tooth enamel. The CPP-ACP, unlike fluoride, can be added
to sugar-containing foods as well as oral care products for the control
of dental caries.
[Back to top] New Aspects
of Angiotensin Receptor Regulation: Implications for Other Seven Transmembrane-Spanning
Receptors. Walter G. Thomas.
Phosphorylation and internalization acutely regulate seven transmembrane-spanning,
G protein-coupled receptors. Additional signalling and regulatory mechanisms
have been recently proposed, including association of receptors with novel
cytoplasmic proteins and a capacity of receptors to isomerize between multiple
"active" states. This short review will introduce these mechanisms using
receptors for the peptide hormone, angiotensin II, as a model for other
G-protein coupled receptors.
[Back to top] Recent Applications
of Instrumental Biosensors for Protein and Peptide Structure-Function Studies.
Bruno Catimel, Teresa Domagala, Maureen Nerrie, Janet Weinstock, Sara White,
Helen Abud, Joan Heath and Edouard Nice.
Since the introduction in the early 1990's of a novel biosensor technology
that measures changes in refractive index at or near a sensor surface,
the technique has been rapidly embraced by the biological research community
to measure a wide range of biomolecular interactions. We will review some
recent applications of this technology including preparative ligand fishing
and cell-based studies, and discuss the relative merits of different instruments
for various applications.
[Back to top] Applications of
NMR in Drug Design: Structure-Activity Relationships in Disulfide-Rich Peptides.
David J. Craik.
NMR is a powerful technique for determining structures of biologically active
molecules in solution. In recent years our laboratory has focussed on the structure
determination of small disulfide-rich proteins from both plants and animals
which are valuable targets in drug design applications. This article will review
these structural studies and their implications in drug design.