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.
MeSH terms
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Amino Acid Sequence
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Animals
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Bone Marrow Cells
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Cell Line
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Colony-Forming Units Assay
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Dose-Response Relationship, Drug
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Hematopoiesis / drug effects*
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Hematopoietic Cell Growth Factors / biosynthesis*
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / drug effects
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Mice
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Mice, Inbred BALB C
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Molecular Structure
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Oligopeptides / administration & dosage
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Oligopeptides / chemical synthesis*
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Oligopeptides / chemistry*
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Oligopeptides / pharmacology*
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Picolinic Acids / administration & dosage
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Picolinic Acids / chemical synthesis*
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Picolinic Acids / pharmacology
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Stromal Cells / drug effects
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Stromal Cells / metabolism
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Structure-Activity Relationship
Substances
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Hematopoietic Cell Growth Factors
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Oligopeptides
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Picolinic Acids
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picolinoyl-seryl-aspartyl-picolinoyl-seryl-aspartyl-2,5-diaminoadipoyl-lysyl-lysine
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SK&F 107647