Structure-activity relationships of novel hematoregulatory peptides

J Med Chem. 1996 Sep 13;39(19):3814-9. doi: 10.1021/jm960099d.

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

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

Substances

  • Hematopoietic Cell Growth Factors
  • Oligopeptides
  • Picolinic Acids
  • picolinoyl-seryl-aspartyl-picolinoyl-seryl-aspartyl-2,5-diaminoadipoyl-lysyl-lysine
  • SK&F 107647