Structure-activity relationships of novel hematoregulatory peptides.
Hematopoiesis is a lifelong cell renewal process regulated by a family of lineage specific hematopoietic growth factors. Several hematopoietic growth factors such as G-CSF, GM-CSF, and M-CSF have been clinically evaluated for enhancement of host defense in normal and immunocompromised patients and for the treatment of infectious diseases. This paper reports the structure-activity relationships of low molecular weight hematoregulatory peptides based on a nonapeptide (1, SK&F 107647). Like the macromolecular growth factors, these peptides modulate host defense. A molecular target for this class of compounds has not yet been identified. However, the structure-activity relationships established by this study implicate a very specific molecular recognition event that is pivotal for the biological activities of 1 and its analogues.
Bhatnagar
P K
PK
Department of Medicinal Chemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA.
Agner
E K
EK
Alberts
D
D
Arbo
B E
BE
Callahan
J F
JF
Cuthbertson
A S
AS
Engelsen
S J
SJ
Fjerdingstad
H
H
Hartmann
M
M
Heerding
D
D
Hiebl
J
J
Huffman
W F
WF
Hysben
M
M
King
A G
AG
Kremminger
P
P
Kwon
C
C
LoCastro
S
S
Løvhaug
D
D
Pelus
L M
LM
Petteway
S
S
Takata
J S
JS
D000595:Amino Acid Sequence; D000818:Animals; D001854:Bone Marrow Cells; D002460:Cell Line; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D006410:Hematopoiesis / Q000187:drug effects*; D016298:Hematopoietic Cell Growth Factors / Q000096:biosynthesis*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009842:Oligopeptides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D010848:Picolinic Acids / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D016298:Hematopoietic Cell Growth Factors; D009842:Oligopeptides; D010848:Picolinic Acids; C101620:picolinoyl-seryl-aspartyl-picolinoyl-seryl-aspartyl-2,5-diaminoadipoyl-lysyl-lysine; C086049:SK&F 107647