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J Med Chem ; 39(19): 3814-9, 1996 Sep 13.
Article in English | MEDLINE | ID: mdl-8809169

ABSTRACT

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.


Subject(s)
Hematopoiesis/drug effects , Hematopoietic Cell Growth Factors/biosynthesis , Oligopeptides/chemistry , Oligopeptides/chemical synthesis , Oligopeptides/pharmacology , Picolinic Acids/chemical synthesis , Amino Acid Sequence , Animals , Bone Marrow Cells , Cell Line , Colony-Forming Units Assay , Dose-Response Relationship, Drug , Hematopoietic Stem Cells/cytology , Hematopoietic Stem Cells/drug effects , Mice , Mice, Inbred BALB C , Molecular Structure , Oligopeptides/administration & dosage , Picolinic Acids/administration & dosage , Picolinic Acids/pharmacology , Stromal Cells/drug effects , Stromal Cells/metabolism , Structure-Activity Relationship
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