PROTEIN

Disampaikan pada MK Farmakologi I

Oleh
Dr. apt. Niken Indriyanti, M.Si
S1 Farmasi
Semester Genap 2023/2024
Tujuan Perkuliahan
1. Mahasiswa mampu memahami konsep dasar protein yang berguna
pada interaksi obat dengan reseptor.
2. Mahasiswa mampu memahami kegunaan protein untuk
menghasilkan efek farmakodinamik
3. Mahasiswa mampu memahami penggunaan protein terapeutik
ACUAN UTAMA

Hlm 25-48
Protein merupakan..
• Molekul besar
• Tersusun dari untaian asam amino
• Ditemukan di setiap sel di dalam tubuh
• Terlibat pada sebagian besar fungsi tubuh dan proses kehidupan
• Rangkaian asam amino dapat ditelusuri pada DNA
Struktur protein-dapat disearch di
https://www.rcsb.org/
• Diklasifikasikan sesuai jumlah asam amino dalam satu untaian, yaitu:
A. Peptida: kurang dari 50 asam amino
• Dipeptida: 2 asam amino
• Tripeptida: 3 asam amino
• Polypeptida: lebih dari 10 asam amino
B. Protein: Lebih dari 50 asam amino
• Biasanya 100 - 10,000 asam amino yang saling terhubung
• Untaian disintesis berdasarkan DNA Spesifik.
• Asam amino terdiri dari C, H, O, N
Perbedaan struktur karbohidrat, lipid,m dan protein
Ikatan peptida menghubungkan asam amino
• Form when the acid group
(COOH) of one amino acid
joins with the amine group
(NH2) of a second amino acid
• Formed through
condensation
• Broken through hydrolysis

https://www.researchgate.net/publication/221913065_Biofunctional_Xerography/figures?
lo=1&utm_source=google&utm_medium=organic
SANGER WAS THE FIRST TO DETERMINE THE
SEQUENCE OF A POLYPEPTIDE

• Mature insulin consists of the 21-residue

A chain and the 30-residue B chain
linked by disulfide bonds. Fred- erick
Sanger reduced the disulfide bonds
(Figure 4–3),
Oxidative cleavage of adjacent
polypeptide chains linked by disulfide
bonds (shaded) by performic acid (left) or
reductive cleavage by β-mercaptoethanol
(right) forms two peptides that contain
cysteic acid residues or cysteinyl residues,
respectively.
CARA PEMURNIAN PROTEIN
• Protein Purity Is Assessed by Polyacrylamide Gel Electrophoresis
(PAGE)
• Isoelectric Focusing (IEF)
Isoelectric Focusing (IEF)

Buffer ionic (Amfolit) dan pemaparan listrik digunakan untuk men-

generate gradien pH dalam matriks gel poliakrilamid.
Protein yang dimasukkan bermigrasi sampai ke matriks sampai ke titik
dimana pH sesuai dengan titik isoelektrik point (pI). pH pada peptide’s
net charge adalah nol.
IEF biasa digunakan dalam satu rangkaian dengan PAGE untuk
elektroforesis 2 dimensi.
Dimensi pertama: pemisalah berdasarkan pl
Dimensi kedua: pemisahan berdasarkan massa relatif (Mr)
Dimensi 1

https://www.nationaldiagnostics.com/2011/09/09/isoelectric-
focusing/
Dimensi 2
Beberapa fungsi protein
1. Mengkatalisis reaksi metabolisme power menghilangkan sementara segmen peptide
cellular motion yang dibutuhkan.
2. Membentuk macromolecular rods and DEFISIENSI NUTRISI/GENETIK yang
cables that provide structural integrity to berhubungan dengan maturase protein
hair, bones, tendons, and teeth misalnya:
Bentuk protein mempengaruhi fungsinya. 3. Creutzfeldt- Jakob disease,
4. scrapie,
Maturasi polipeptida baru menjadi protein yang 5. Alzheimer’s disease,
berfungsi secara biologis memerlukan lekukan 6. and bovine spongiform encephalopathy
spesifik menjadi bentuk 3 dimensi spesifik, atau (mad cow disease).
disebut KONFORMASI.
7. Scurvy represents a nutritional deficiency
Selama proses maturasi, modifikasi that impairs protein maturation.
posttranslational dapat menambahkan
golongan senyawa kimia baru atau
Konformasi vs konfigurasi
Configuration refers to the geometric relationship between a given set
of atoms, for example, those that distinguish L- from D-amino acids.
Interconversion of configurational alternatives requires breaking
covalent bonds.

Conformation refers to the spatial relationship of every atom in a

molecule. Interconversion between conformers occurs without
covalent bond rupture, with retention of configuration, and typically via
rotation about single bonds.
• Globular proteins
Merupakan bentuk dari sebagian besar
enzim.
Lipoproteins and glycoproteins contain
covalently bound lipid and carbohydrate,
respectively.
Myoglobin, hemoglobin, cytochromes,
and many other proteins contain tightly
associated metal ions and are termed
metalloproteins.
Structure of the
Protein
• Four levels of structure
• Primary structure
• Secondary structure
• Tertiary structure
• Quaternary structure

Any alteration in the structure or sequencing changes the shape and

function of the protein
https://biologydictionary.net/protein-structure/
α helix
β sheets.
STRUKTUR TERSIER DAN KUARTERNER

Examples of tertiary structure of pro-

teins.
Top: The enzyme triose phosphate
isomerase.
Note the elegant and symmetrical
arrangement of alternating β sheets and
α helices. (Courtesy of J Richard- son.)

Bottom: Two-domain structure of the

subunit of a homodimeric enzyme, a
bacterial class II HMG-CoA reductase. As
indicated by the numbered residues, the
single polypeptide begins in the large
domain, enters the small domain, and
ends in the large domain. (Courtesy of C
Lawrence, V Rodwell, and C Stauffacher,
Purdue University.)
Denaturasi protein
• Perubahan pada bentuk protein dan fungsinya bisa terjadi akibat:
PANAS, ASAM, BASA, GARAM, GONCANGAN MEKANIK

• STRUKTUR PRIMER TIDAK BERUBAH AKIBAT ADANYA DENATURASI

THREE-DIMENSIONAL STRUCTURE IS DETERMINED
BY X-RAY CRYSTALLOGRAPHY OR BY
NMR SPECTROSCOPY
• X-Ray Crystallography
• Nuclear Magnetic Resonance Spectroscopy
• Molecular Modeling menggunakan aplikasi komputer
Hemoglobin dan myoglobin

Oxygen-binding curves of both hemoglobin and myoglobin. Arterial oxygen tension is about
100 mm Hg; mixed venous oxygen tension is about 40 mm Hg; capillary (active muscle) oxygen tension is about
20 mm Hg; and the minimum oxygen tension required for cytochrome oxidase is about 5 mm Hg. Association of
chains into a tetrameric structure (hemoglobin) results in much greater oxygen delivery than would be possible
with single chains.
Pelepasa oksigen dan pengambilan CO2
dalam jaringan

https://www.google.com/url?sa=i&url=https%3A%2F
%2Fwww.quora.com%2FHow-is-carbon-dioxide-transported-
from-tissues-to-lungs&psig=AOvVaw0LQrSI2-FaWuGJcy_3KA-
b&ust=1707809795906000&source=images&cd=vfe&opi=8997
8449&ved=0CBIQjRxqFwoTCLCOzbOlpYQDFQAAAAAdAAAAABA
PROTEIN TERAPEUTIK

https://www.google.com/url?sa=i&url=https%3A%2F
https://www.google.com/url?
%2Fwww.researchgate.net%2Ffigure%2FCrystal-structures-of-
sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwjGvLD
A-recombinant-human-insulin-Humulin-R-PDB-
JiKyEAxVWR2wGHYq-DzA4ChAWegQIAhAB&url=https%3A%2F
4F0N_fig4_333903037&psig=AOvVaw0sdQcSbV6yER6mUmerm
%2Fs2.smu.edu%2Fjbuynak%2FProtein_Therapeutics--
S16&ust=1708042911975000&source=images&cd=vfe&opi=89
Xiao_Yu.ppt&usg=AOvVaw3UhQGz6TJRFgKS330pY9cs&opi=899
978449&ved=0CBIQjRxqFwoTCMi0q-
78449
What is Protein therapeutics?

It is currently estimated that there are 25,000–40,000 different

genes in the human genome, viewed from the perspective of
disease mechanisms, as disease may result
when any one of these proteins contains
mutations or other abnormalities, so it
gives a tremendous opportunity for
Protein therapeutics to alleviate
these disease.
Why protein therapeutics?

Proteins cannot be mimicked by simple chemical compounds.

There is often less potential for protein therapeutics to interfere

with normal biological processes and cause adverse effects.

It is often well tolerated and are less likely to elicit immune responses.

Provide effective replacement treatment without the need for gene therapy

Time of protein therapeutics may be faster

The Evolution of Protein Therapeutics : A Timeline

1953 First accurate model of DNA suggested

1982 Human insulin, created using recombinant DNA technology

1986 Interferon alfa and muromonab-CD3 approved

1993 CBER's Office of Therapeutics Research and Review (OTRR) formed

1997 First whole chimeric antibody, rituximab, and first humanized
antibody, daclizumab, approved

2002 Market for biotechnology products represents approximately $30

billion of $400 billion in yearly worldwide pharmaceutical sales

2006 An inhaled form of insulin (Exubera) approved, expanding protein

products into a new dosage form.
Classification of protein therapeutics

Group I: protein therapeutics with enzymatic or regulatory activity

Group II : protein therapeutics with special targeting activity

Group III : protein vaccines

Group IV : protein diagnostics

Protein therapeutics replacing a protein that is deficient or abnormal (Group Ia)*
Protein therapeutics augmenting an existing pathway (Group Ib)*
Protein therapeutics providing a novel function or activity (Group Ic)
Protein therapeutics that interfere with a molecule or organism (Group II a)*
Protein therapeutics that deliver other compounds or proteins (Group II b)
Protein vaccines (Group III )*
Protein diagnostics (Group IV )
TUGAS TERSTRUKTUR
TUGAS KELOMPOK:

Buat tulisan dan ilustrasi cara penggunaan produk protein (slide 30-36)
Ketua kelas mengatur kelompok sesuai urutan angkatan dan NIM mahasiswa.
1 kelas dibagi menjadi 7 kelompok
Tabel dalam 1 slide ppt dikerjakan 1 kelompok.
Dikirim ke link
https://drive.google.com/drive/folders/1-BOW35keLjMKcTBnfI6iqkVwx8XJTQhn?usp=drive_link
Paling lambat 29 Februari 2023 pukul 16.00 WITA
Contoh format tugas terlampir
Dibuat dalam format Ms WORD, landscape/portrait bebas, ukuran kertas A4
Silahkan mengakses data produk, lihat di bagian dosage and administration sebagai acuan. Contoh:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/alemmil050701LB.htm#dose
Contoh: Cara penggunaan produk insulin
•