Chapter 1
Introduction
1.1 Introduction of Protein-Protein Interactions
1.1.1 Significance of Studying Protein-Protein Interactions
Protein-protein interactions (PPIs) play important roles in cell life activities, such
as signal transduction, cell cycle, immune system, gene regulation, and so on [1–3].
The size of protein-protein interactions is one of the important indicators to measure
the complexity of life. Humans contain over 650,000 pairs of PPIs. The study of PPIs
is of great significance, these benefits include but not limited to:
1. To help better understand system biology;
2. To provide novel strategies for disease diagnosis and treatment;
3. To aid the development of new drugs.
The development of PPIs targeting pharmaceuticals is significant, however, PPIs
are traditionally considered undruggable by small-molecular drugs. Despite smallmolecular drugs that can penetrate cell membranes readily, their specific binding to
PPIs is a huge challenge and is currently an important issue in the chemical biology
community. Unlike active catalytic pockets displayed in enzymes, the interface of
protein-protein interaction is large as well as flat and lacks obvious binding pockets.
To design effective PPI inhibitors, it requires molecules to meet the following conditions: providing continuous non-covalent interactions with target proteins; the contact
area with protein is greater than 800 Å
2 , a value significantly larger than the size of
a traditional substrate-enzyme binding pocket. Notably, although the contact area of
PPIs is relatively large, the key interactions are usually dominated by a few of key
amino acids, which are designated as ‘hot spots’ [4, 5]. This truth makes the rational
design of PPI inhibitors achievable and possible. Indeed, the current rationale in
designing PPI inhibitors is to synthesize peptide mimetics that reproduce the hot
© Springer Nature Singapore Pte Ltd. 2021
K. Hu, Development of In-Tether Carbon Chiral Center-Induced
Helical Peptide, Springer Theses,
https://doi.org/10.1007/978-981-33-6613-8_1
1
Introduction
1.1 Introduction of Protein-Protein Interactions
1.1.1 Significance of Studying Protein-Protein Interactions
Protein-protein interactions (PPIs) play important roles in cell life activities, such
as signal transduction, cell cycle, immune system, gene regulation, and so on [1–3].
The size of protein-protein interactions is one of the important indicators to measure
the complexity of life. Humans contain over 650,000 pairs of PPIs. The study of PPIs
is of great significance, these benefits include but not limited to:
1. To help better understand system biology;
2. To provide novel strategies for disease diagnosis and treatment;
3. To aid the development of new drugs.
The development of PPIs targeting pharmaceuticals is significant, however, PPIs
are traditionally considered undruggable by small-molecular drugs. Despite smallmolecular drugs that can penetrate cell membranes readily, their specific binding to
PPIs is a huge challenge and is currently an important issue in the chemical biology
community. Unlike active catalytic pockets displayed in enzymes, the interface of
protein-protein interaction is large as well as flat and lacks obvious binding pockets.
To design effective PPI inhibitors, it requires molecules to meet the following conditions: providing continuous non-covalent interactions with target proteins; the contact
area with protein is greater than 800 Å
2 , a value significantly larger than the size of
a traditional substrate-enzyme binding pocket. Notably, although the contact area of
PPIs is relatively large, the key interactions are usually dominated by a few of key
amino acids, which are designated as ‘hot spots’ [4, 5]. This truth makes the rational
design of PPI inhibitors achievable and possible. Indeed, the current rationale in
designing PPI inhibitors is to synthesize peptide mimetics that reproduce the hot
© Springer Nature Singapore Pte Ltd. 2021
K. Hu, Development of In-Tether Carbon Chiral Center-Induced
Helical Peptide, Springer Theses,
https://doi.org/10.1007/978-981-33-6613-8_1
1