Guanosine pentaphosphate (ppGpp)

Guanosine pentaphosphate (ppGpp) is a purine nucleotide derivative and a central bacterial signaling molecule, classified as an alarmone, that mediates the stringent response in prokaryotes[1][3][5]. In response to nutrient or environmental stresses, ppGpp rapidly accumulates and reorganizes gene expression by altering transcriptional and translational profiles[1][3][7]. ppGpp regulates essential processes: it binds bacterial RNA polymerase to inhibit rRNA and tRNA synthesis, controls DNA replication, inhibits translation initiation, and coordinates cellular metabolism to improve survival under adverse conditions by promoting dormancy and stress resistance[1][5][7]. Collectively, these functions underlie processes such as antibiotic persistence, immune evasion, and virulence in pathogenic bacteria[5]. ppGpp is most prominent in bacteria but is also found in plant chloroplasts[1][6]. While highly conserved and studied as a bacterial physiological and virulence regulator, ppGpp itself is not conventionally considered a therapeutic target as a receptor, enzyme, transporter, or transcription factor. However, enzymes regulating its synthesis and degradation (\"RelA\", \"SpoT\" in Gram-negatives; \"Rel\" in Gram-positives)[3][8], rather than ppGpp directly, are being investigated as potential antimicrobial targets due to their roles in pathogen adaptation and persistence. The abbreviation (p)ppGpp refers to both guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), which have similar but distinct roles[1][3][5]. While not a classical target by strict modern pharmacological definitions, understanding and modulating the enzymes responsible for ppGpp metabolism may be therapeutically relevant, especially in fighting bacterial persistence and antibiotic tolerance[5].

Other names

guanosine 3',5'-bis(diphosphate)"magic spot" nucleotide(p)ppGpp (collective term for ppGpp and pppGpp)stringent response alarmone

Not applicable (ppGpp is not a conventional drug target; it is a signaling metabolite)